© 1997 American Heart Association, Inc.
Articles |
Lipid Oxidation Products Have Opposite Effects on Calcifying Vascular Cell and Bone Cell Differentiation
A Possible Explanation for the Paradox of Arterial Calcification in Osteoporotic Patients
Presented in part at the 68th Scientific Sessions of the American Heart Association, Anaheim, Calif, November 13-16, 1995.
From the Division of Cardiology, Department of Medicine (F.P., A.D.M., J.B., Y.T., L.L.D.) and Department of Pathology (N.L., A.D.W., J.A.B.), University of California at Los Angeles School of Medicine.
Correspondence to F. Parhami, PhD, Division of Cardiology, UCLA School of Medicine, 47-123 Center for the Health Sciences, 10833 Le Conte Ave, Los Angeles, CA 90095. E-mail fparhami{at}medicine.medsch.ucla.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract Atherosclerotic calcification and osteoporosis often coexist in patients, yielding formation of bone mineral in vascular walls and its simultaneous loss from bone. To assess the potential role of lipoproteins in both processes, we examined the effects of minimally oxidized low-density lipoprotein (MM-LDL) and several other lipid oxidation products on calcifying vascular cells (CVCs) and bone-derived preosteoblasts MC3T3-E1. In CVCs, MM-LDL but not native LDL inhibited proliferation, caused a dose-dependent increase in alkaline phosphatase activity, which is a marker of osteoblastic differentiation, and induced the formation of extensive areas of calcification. Similar to MM-LDL, oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (ox-PAPC) and the isoprostane 8-iso prostaglandin E2 but not PAPC or isoprostane 8-iso prostaglandin F2
induced
alkaline phosphatase activity and differentiation of CVCs. In contrast,
MM-LDL and the above oxidized lipids inhibited differentiation of the
MC3T3-E1 bone cells, as evidenced by their stimulatory effect on
proliferation and their inhibitory effect on the induction
of alkaline phosphatase and calcium uptake. These results suggest that
specific oxidized lipids may be the common factors underlying the
pathogenesis of both atherosclerotic calcification and osteoporosis.
Key Words: calcification • atherosclerosis • oxidized lipids • calcifying vascular cells • alkaline phosphatase
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Calcium deposits, consisting of the bone mineral apatite, are extremely common in atherosclerotic lesions and are associated with clinical complications such as myocardial infarction, impaired vascular tone, dissection in angioplasty, poor surgical outcome, and coronary insufficiency due to loss of aortic recoil.1 2 The mechanism of vascular calcification is not yet established; however, recent evidence implicates factors important in bone mineralization3 including matrix vesicles,4 bone morphogenetic protein-2,5 osteopontin,6 osteocalcin,7 and collagen I,8 all of which have been identified in atherosclerotic plaque.
We previously identified cloned subpopulations of aortic medial cells, termed CVCs, which spontaneously calcify in vitro and express osteoblast markers such as alkaline phosphatase, osteopontin, osteocalcin, osteonectin, and collagen I.9 This in vitro model was confirmed and enhanced by Shioi et al.10 CVC calcified nodules express the bone/liver/kidney isoform of alkaline phosphatase, which is widely used as an early marker of osteoblastic differentiation.11
The role of the ectoenzyme alkaline phosphatase associated with matrix vesicles in osteoblast differentiation and mineralization is most likely the hydrolysis of ester phosphates at sites of mineralization, providing ionic phosphate for incorporation into calcium-phosphate mineral.12 Previous studies, using the alkaline phosphatase inhibitor levamisole, have shown its importance in the commitment of bone preosteoblasts to mineralization.13 Alkaline phosphatase may also inactivate pyrophosphate, an inhibitor of hydroxyapatite formation,12 and it may have an intracellular function14 important in regulating cellular differentiation.
The role of LDL oxidation products and their accumulation in the vessel wall during atherosclerotic lesion formation is well established.15 16 Since calcium deposits are found as early as the fatty streak stage,17 often in close association with lipids,18 19 we hypothesized that oxidized lipids have a functional role in osteoblastic differentiation of vascular cells. Further evidence for the possible role of lipids in calcification is the inhibition of calcification in delipidated heart valves.20 21 MM-LDL is a potent atherogenic molecule with biologic activity in vitro and in vivo.22 23 Watson et al24 reported that ox-PAPC has biologic activity similar to MM-LDL. In 1996, Morrow and Roberts25 reported that prostaglandin-like isoprostanes, formed by the free radical–catalyzed peroxidation of arachidonic acid, are produced in vivo in humans and may contribute to oxidative injury. Isoprostanes have also been found in cell- and metal-oxidized LDL26 and may at least partially account for its biologic activity.
Osteoporotic loss of bone is attributed to abnormalities in the balance of bone remodeling, both increased bone resorption by osteoclasts and decreased bone formation by osteoblasts.27 Since osteoporosis commonly coexists with atherosclerotic calcification,28 29 30 31 32 common factors may be responsible in the pathogenesis of both diseases.
In the present study, we used alkaline phosphatase as a marker for osteoblastic differentiation of CVCs to examine the role of the above oxidized lipids and lipoprotein in in vitro vascular calcification. For comparison, the same treatments were applied to MC3T3-E1, a preosteoblast calvarial cell line that has been used extensively for bone cell physiological studies.33 MC3T3-E1 cells follow the same process of osteoblastic differentiation as osteoblasts in vivo, including inhibition of proliferation and upregulation of alkaline phosphatase at the onset of differentiation.33 34 Results showed a strong, dose-dependent positive effect of MM-LDL, ox-PAPC, and the isoprostane iso-PGE2 on osteoblastic differentiation of vascular cells but reciprocal effects on MC3T3-E1. These results led us to speculate that lipid accumulation and oxidation in the subendothelial space of the extensive vasculature in bone may inhibit differentiation of adjacent preosteoblasts, thus contributing to osteoporosis and accounting at least in part for the paradox of atherosclerotic calcification and osteoporosis occurring together in many patients.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Cell Cultures
CVC clones were isolated from cultures of BASMCs in which multicellular nodules spontaneously appeared as previously described.9 CVCs were grown in DMEM (Irvine Scientific) containing 15% fetal bovine serum (Hyclone Labs) supplemented with sodium pyruvate (1 mmol/L), penicillin (100 U/mL), and streptomycin (100 U/mL), all from Irvine Scientific. MC3T3-E1 mouse preosteoblast cell line (from Riken Cell Bank) was grown in
MEM
(Irvine Scientific) containing 10% FCS, 3 mmol/L
ß-glycerophosphate (Sigma), and 25 µg/mL ascorbic acid and
supplemented as indicated for DMEM above. The presence of
ß-glycerophosphate and ascorbic acid significantly enhances
calcification in MC3T3-E1 cultures. Isoprostanes were purchased from
Cayman Chemical.
Alkaline Phosphatase Assay
A cell-associated alkaline phosphatase activity assay was
performed with a modification of the alkaline phosphatase assay kit
from Sigma. Cells were cultured in 24-well tissue-culture plates. After
treatments with test agents, cells were rinsed twice with PBS and
scraped into 200 µL of lysis buffer (0.2% NP-40 in 1 mmol/L
MgCl2) with a rubber policeman and sonicated for 10
seconds. Next, 1 mL of reaction mixture was added to each well.
Reaction mixture was 221 alkaline buffer (Sigma): stock substrate
solution 1:1. Stock substrate solution was prepared by dissolving the
contents of a 100-mg capsule of Sigma 104 phosphatase substrate in 25
mL of ddH2O. This mixture was then incubated for 30 minutes
at 37°C. The yellow color was indicative of alkaline phosphatase
activity. The reaction was stopped by the addition of 12 µL of 1N
NaOH to each well, and absorbance was determined at 405 nm. Alkaline
phosphatase activity was calculated using p-nitrophenol as a
standard, according to the kit's instructions (Sigma). Results were
normalized to total protein determined using the Bio-Rad protein assay
solution (Bio-Rad Laboratories).
Lipoprotein and Lipids
Human LDL was isolated by density-gradient
centrifugation of serum and stored in
phosphate-buffered 0.15 mol/L NaCl containing 0.01% EDTA. MM-LDL was
prepared by iron oxidation of human LDL as previously
described.35 Minimal oxidation of LDL resulted in a
twofold to threefold increase in conjugated dienes and 2 to 3 nmol of
thiobarbituric acid–reactive substances per milligram of
cholesterol after dialysis. The concentrations of
lipoprotein used in this study are reported in micrograms of protein.
PAPC (Sigma) was oxidized as described previously.24
Briefly, PAPC was first dried under argon and exposed to air for 48
hours at room temperature under sterile conditions. The ox-PAPC was
resuspended in chloroform and stored at -80°C covered with
argon.
Von Kossa Staining for Calcification
Cell monolayers were fixed in 0.1%
glutaraldehyde in PBS for 15 minutes at room
temperature. Cells were then washed twice with ddH2O and
incubated with 5% silver nitrate for 30 minutes at room temperature in
the dark. Silver nitrate was removed and cells were rinsed twice with
ddH2O. Next, cultures were air dried and exposed to
sunlight until color development was complete. Cells were rinsed with
ddH2O and prepared for phase microscopy.
[3H]Thymidine Incorporation
Cells were cultured in 24-well plates and treated with or
without agonists. During the last 24 hours of treatments, cells were
pulsed with 1 µCi/mL [3H]thymidine (Amersham). The
incorporated label was extracted and quantitated as previously
described.36
45Ca Accumulation
45Ca accumulation assay was performed as described
previously.37 Briefly, cells were cultured in 24-well
plates, in the presence or absence of oxidized lipids for 2 weeks.
45CaCl2 (Amersham) was then added at 0.5
µCi/mL. After 48 hours of incubation with the
45CaCl2, the medium was removed and the cells
were rinsed twice with PBS and scraped in 0.3 mL of PBS, into vials
containing 0.2 mL of perchloric acid. After vortexing, 0.4 mL of 3%
hydrogen peroxide was added to each sample and incubated at 80°C for
1 hour. Samples were then dissolved in 0.6 mL of ethylene glycol
monoethyl ether (Sigma) and vortexed, and the radioactivity accumulated
was quantitated by scintillation counting. 45Ca
accumulation measured by this technique is mainly matrix bound, since
similar findings are obtained with
Tx-100–permeabilized cells in which ionic calcium is
removed.
Quantitation of Areas of Nodules
The area of nodules in control or MM-LDL–treated CVC cultures
was quantitated by computer-assisted analysis of phase-contrast
photographs of representative visual fields (x40).
Photomicrographs were then scanned and the areas of nodules per field
measured using the NIH image program. The areas (pixels) are reported
as the mean±SD of at least five fields.
Statistical Analysis
Computer-assisted statistical analyses were performed
using the ANOVA program.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Effect of MM-LDL on CVC Morphology and Nodules
After 3 days of treatment with MM-LDL, CVC morphology changed distinctly from a thin fibroblastic to a cuboidal form (Fig 1A
and 1B). A similar morphological change occurs in
differentiation of preosteoblasts into mature
osteoblasts.38 39 After 10 days of treatment, large areas
of cellular condensations appeared in the MM-LDL–treated cultures as
opposed to the typical small, round focal condensations seen in the
control cultures (Fig 1C and 1D). This finding is also similar to the
process of cell aggregation/condensation reported previously during
bone and cartilage cell differentiation and mineralization in vitro and
in vivo.40 Quantitation of the areas of condensation in
control versus MM-LDL–treated cultures showed a 145% increase with
MM-LDL treatment (control, 14 140±4378 pixels; MM-LDL, 34 591±7625
pixels; P<.001; n=5). After 3 weeks, von Kossa staining,
though not quantitative, showed a less dense but substantially larger
area of positively stained calcifying condensations in the
MM-LDL–treated versus control cultures (Fig 1E and 1F). In addition,
condensations in treated cultures were broader and more irregularly
shaped than the condensations in control cultures, which were small,
focal nodules as previously reported (Fig 1C and 1D).9
Native LDL did not have effects similar to MM-LDL on CVC morphology or
von Kossa staining (data not shown). MM-LDL had no effect on BASMC
morphology, in contrast to its effects on CVCs derived from BASMC
cultures (data not shown).
|
Relationship of Alkaline Phosphatase Activity and CVC Nodule
Formation
Induction of alkaline phosphatase is important in the
differentiation of osteoblasts.11 Similar induction of
alkaline phosphatase activity occurs during CVC differentiation, at the
onset of the cellular condensation (Fig 2).
|
Effect of MM-LDL on Alkaline Phosphatase Activity in CVCs and
MC3T3-E1
To determine whether MM-LDL modulates CVC differentiation, we
treated CVCs for 6 days with MM-LDL and found a significant
dose-dependent induction of alkaline phosphatase activity (Fig 3). This effect persisted for at least 26 days of
treatment, whereas even prolonged incubation with native LDL did not
induce alkaline phosphatase activity in CVCs (Fig 4A).
Alkaline phosphatase activity in BASMCs was not affected by MM-LDL
(data not shown). We also examined the effect of MM-LDL on alkaline
phosphatase activity of MC3T3-E1 bone preosteoblasts. Unexpectedly, in
contrast to the response of CVCs, the expression of alkaline
phosphatase activity was inhibited by MM-LDL treatment (Fig 4B),
suggesting that the normal differentiation of these cells is inhibited
by MM-LDL.
|
|
To assess the importance of the duration of MM-LDL exposure, CVCs were
incubated for different times with MM-LDL, rinsed, and fed with fresh
medium for the 6-day total culture period. Treatment for 24 hours or
less had no effect on alkaline phosphatase, whereas a 6-day treatment
induced its activity (Fig 5), suggesting that further
modification, internalization, or processing of MM-LDL may be necessary
for this effect. In addition, similar experiments showed that a minimum
of 3 days of incubation with MM-LDL is required for the induction of
alkaline phosphatase activity (data not shown).
|
Effect of Ox-PAPC and Iso-PGE2 on Alkaline
Phosphatase Activity
Since ox-PAPC has biologic activity similar to
MM-LDL,24 we tested the effect of ox-PAPC on CVCs. The
results showed that similar to MM-LDL, ox-PAPC caused a dose-dependent
activation of alkaline phosphatase activity in these cells, with
greater potency than MM-LDL (Fig 6); PAPC itself did not
have similar effects. Kinetic studies of the effect of ox-PAPC showed
that continuous incubation of CVCs for at least 2 days was necessary
for induction of alkaline phosphatase activity to the level induced
after 6 days of treatment with MM-LDL (data not shown). Ox-PAPC also
had an inhibitory effect on the induction of alkaline
phosphatase activity in MC3T3-E1 (data not shown).
|
Since isoprostanes are present in oxidized LDL26 as
well as in oxidatively damaged tissues,25 we tested the
effect of purified iso-PGE2 on CVCs. Similar to the other
oxidized lipids tested, iso-PGE2 at 1 to 50 µmol/L
caused a significant dose-dependent induction of alkaline phosphatase
activity and morphological changes in CVCs (Fig 7A).
Isoprostane iso-PGF2, a stereoisomer of
PGF2, did not induce alkaline phosphatase activity in CVCs
(Fig 7A), suggesting that the effect is specific to
iso-PGE2. Iso-PGE2 did not have similar effects
on BASMCs (data not shown). Similar to MM-LDL and ox-PAPC,
iso-PGE2 but not iso-PGF2 had an
inhibitory effect on the induction of alkaline phosphatase
activity in MC3T3-E1 preosteoblasts (Fig 7B), suggesting the inhibition
of normal differentiation in these cells.
|
Effect of MM-LDL on DNA Synthesis
Differentiation of osteoblastic cells is associated with the
inhibition of proliferative activity.11 As a measure of
proliferation, we examined the effect of MM-LDL on DNA synthesis in
CVCs and MC3T3-E1 by the method of [3H]thymidine
incorporation. Treatment of CVCs at 80% confluence with 250 µg/mL
MM-LDL or native LDL for 24 hours in the presence of
[3H]thymidine showed no significant change in the
incorporation of the label with either agent (data not shown). However,
after 6 days of treatment with MM-LDL, there was a 40% inhibition in
DNA synthesis; treatment with native LDL had no effect (Fig 8A). In further contrast to the response of CVCs, MM-LDL
stimulated DNA synthesis in MC3T3-E1 cells (Fig 8B).
|
Effect of MM-LDL on MC3T3-E1 Calcification
The effect of MM-LDL on calcification in the MC3T3-E1 cultures was
determined by von Kossa staining and 45Ca accumulation
assay.37 After 2 weeks in culture, von Kossa staining
showed extensive calcification, which was inhibited by MM-LDL
incubation (Fig 9A). The inhibitory effect
of MM-LDL on calcification of MC3T3-E1 was also shown by the inhibition
of 45Ca accumulation (Fig 9B). This was further evidence
that in the presence of MM-LDL, the differentiation and hence
mineralization of MC3T3-E1 cells was inhibited.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The paradox of osteoporosis in the face of atherosclerotic calcification,28 29 30 31 32 involving bone mineral loss in one location and its formation in another, suggests that neither process is attributable to simple systemic calcium excess or deficiency. The present study is the first to report on the possible role of oxidized lipids, which have an established role in atherogenesis,16 in both vascular calcification and osteoporosis.
On the basis of characteristic morphological changes, inhibition of proliferation, induction of alkaline phosphatase, and formation of extensive cellular condensations containing calcium mineral, we determined that treatment of cloned CVCs with MM-LDL but not native LDL induced osteoblastic differentiation. We have consistently observed that in long-term CVC cultures, calcification is limited to areas of abundant matrix within the condensation and eventually covers the entire condensation. We refer to these areas as being "competent for calcification." Although the total area competent for calcification was increased by MM-LDL, the calcification appeared less dense in treated versus control cultures. This observation suggests that MM-LDL treatment may prolong the stage of matrix maturation,11 when matrix competent for calcification is formed. Therefore, we anticipate that with longer time in culture, dense calcification would appear throughout the condensation network in MM-LDL–treated cultures. However, due to time limitations on cell survival in culture, such prolonged experiments are not possible. It is also possible that MM-LDL can induce osteoblastic differentiation of CVCs without an immediate effect on calcification. Unexpectedly, in contrast to CVCs, treatment of preosteoblastic MC3T3-E1 cells with MM-LDL inhibited their differentiation, as indicated by the stimulation of proliferation, inhibition of alkaline phosphatase activity, and inhibition of calcification. Similar to the effects of MM-LDL, ox-PAPC and iso-PGE2 also induced prodifferentiation and antidifferentiation effects on CVCs and MC3T3-E1 bone preosteoblasts, respectively. These observations suggest that isoprostanes may be important molecules in vascular disease and require further attention. In addition, the formation of oxidized phospholipids in the plasma membrane of intact or dying cells in response to oxidative stress41 may contribute to the earliest events in ectopic calcification under oxidative stress.
The in vivo relevance of the effects of oxidized lipids on osteoblastic
cells may not be immediately apparent. However, given that bone is a
highly vascular tissue and its building block, the osteon, closely
resembles the artery wall (Fig 10), it is clear that
lipoprotein accumulation in the subendothelial spaces
of bone could affect osteoblasts. The osteon is centered on an
endothelial cell–lined blood lumen surrounded by a
subendothelial space containing matrix and
fibroblast-like cells, which is in turn surrounded by preosteoblasts
and osteoblasts occupying a position analogous to smooth muscle cells
in the artery wall. Trabecular bone osteoblasts also
interface with a vascular space, the bone marrow, and its
subendothelial spaces. Since
histological studies have shown that
arteriosclerotic changes, including lipid
de-position, occur in bone vasculature,42 we speculate
that blood vessels in bone may also be susceptible to lipoprotein entry
into the subendothelial space. In addition, similar to
the correlation between LDL concentrations in the arterial
intima and in plasma, equilibration of LDL concentrations in bone
interstitial space with plasma levels might be anticipated.
Products of lipoprotein oxidation may then inhibit the
differentiation and activity of osteogenic cells, as well as possibly
induce migration of monocytes, which in bone tissue differentiate into
bone-resorbing osteoclasts. Recently, the stimulatory effect of the
antioxidant vitamin E on bone formation in chicks fed a high-fat diet
has been reported,43 suggesting a correlation between
induction of normal bone growth and inhibition of lipid oxidation.
|
Although atherosclerotic vascular calcification occurs earlier in men than in women and the opposite holds for osteoporosis, these differences may be due to the higher peak bone mass in men and the multiple modulating effects of gonadal and steroidal hormones. In addition, in the age range when osteoporosis afflicts women (after menopause), vascular calcification and atherosclerotic disease occur as often as in men.44
We conclude that specific oxidized lipids have reciprocal effects on CVCs and bone cells in vitro. Therefore, we suggest that oxidized lipid accumulation in the subendothelial space of arteries promotes arterial calcification and that its accumulation in the subendothelial space of skeletal bone arteries inhibits bone mineral formation. These events may account for the paradox of atherosclerotic calcification in the face of osteoporosis.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This work was supported in part by NIH grants HL30568 and HL43379, as well as by the Oberkotter Research Foundation, the Stein-Oppenheimer Research Foundation, and the Streisand Research Fund established by The Lincy Foundation.
Received September 25, 1996; accepted January 7, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Demer LL. A skeleton in the atherosclerosis closet. Circulation. 1995;92:2029-2032.
2.
Baron MG. Significance of coronary
artery calcification. Radiology. 1994;192:613-614.
3. Doherty TM, Detrano RC. Coronary arterial calcification as an active process: a new perspective on an old problem. Calcif Tissue Int. 1994;54:224-230. [Medline] [Order article via Infotrieve]
4. Tanimura A, McGregor DH, Anderson HC. Matrix vesicles in atherosclerotic calcification. Proc Soc Exp Biol Med. 1983;172:173-177. [Medline] [Order article via Infotrieve]
5. Bostrom K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993;91:1800-1809.
6. Giachelli CM, Bae N, Almeida M, Denhardt DT, Alpers CE, Schwartz SM. Osteopontin is elevated during neointima formation in rat arteries and is a novel component of human atherosclerotic plaques. J Clin Invest. 1993;92:1686-1696.
7.
Ginsberg B, van Haarlem LJM, Soute BAM, Ebberink RHM,
Vermeer C. Characterization of a GLA-containing protein from
calcified human atherosclerotic plaques.
Arteriosclerosis. 1990;10:991-995.
8.
Katsuda S, Okada Y, Minamoto T, Oda Y, Matsui Y,
Nakanishi I. Collagens in human
atherosclerosis. Arterioscler
Thromb. 1992;12:494-502.
9. Watson KE, Bostrom K, Ravindranath R, Lam T, Norton B, Demer LL. TGF-ß1 and 25-hydroxycholesterol stimulate osteoblast-like cells to calcify. J Clin Invest. 1994;93:2106-2113.
10.
Shioi A, Nishizawa Y, Jono S, Koyama H, Hosoi M, Morii
H. ß-Glycerophosphate accelerates calcification in cultured
bovine vascular smooth muscle cells. Arterioscler Thromb
Vasc Biol. 1995;15:2003-2009.
11.
Stein GS, Lian JB. Molecular mechanisms
mediating proliferation/differentiation interrelationships during
progressive development of the osteoblast phenotype.
Endocr Rev. 1993;14:424-442.
12. Anderson HC. Molecular biology of matrix vesicles. Clin Orthop. 1995;314:266-280.
13. Klein BY, Gal I, Segal S. Studies of the levamisole inhibitory effect on rat stromal-cell commitment to mineralization. J Cell Biochem. 1993;53:114-121. [Medline] [Order article via Infotrieve]
14. Narisawa S, Hofmann MC, Ziomek CA, Millan JL. Embryonic alkaline phosphatase is expressed at M-phase in the spermatogenic lineage of the mouse. Development. 1992;116:159-165. [Abstract]
15. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low density lipoproteins that increase its atherogenicity. N Engl J Med. 1989;320:915-924. [Medline] [Order article via Infotrieve]
16. Witztum JL, Steinberg D. Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest. 1991;88:1785-1792.
17. Guyton JR, Klemp KF. Transitional features in human atherosclerosis. Am J Pathol. 1993;143:1444-1457. [Abstract]
18.
Stary HC. The sequence of cell and matrix
changes in atherosclerotic lesions of coronary arteries in the
first forty years of life. Eur Heart J. 1990;11:3-19.
19. Hirsch D, Azoury R, Sarig S, Kruth HS. Colocalization of cholesterol and hydroxyapatite in human atherosclerotic lesions. Calcif Tissue Int. 1993;52:94-98. [Medline] [Order article via Infotrieve]
20. Jorge-Herrero E, Fernandez P, De la Torre N, Escudero C, Garcia-Paez JM, Bujan J, Castillo-Olivares JL. Inhibition of the calcification of porcine valve tissue by selective lipid removal. Biomaterials. 1994;15:815-820. [Medline] [Order article via Infotrieve]
21. Rossi MA, Braile DM, Teixeira DR, Souza D, Peres LC. Lipid extraction attenuates the calcific degeneration of bovine pericardium used in cardiac valve bioprostheses. J Exp Pathol. 1990;71:187-196.
22. Berliner JA, Territo MC, Sevanian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM. Minimally modified low density lipoprotein stimulates monocyte-endothelial interactions. J Clin Invest. 1990;85:1260-1266.
23. Liao F, Berliner JA, Mehrabian M, Navab M, Demer LL, Lusis AJ, Fogelman AM. MM-LDL is biologically active in vivo in mice. J Clin Invest. 1991;87:2253-2257.
24. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. J Clin Invest. 1995;96:2882-2891.
25. Morrow JD, Roberts LJ. The isoprostanes: current knowledge and directions for future research. Biochem Pharmacol. 1996;51:1-9. [Medline] [Order article via Infotrieve]
26. Gopaul NK, Nourooz-Zadeh J, Mallet AI, Anggard EE. Formation of F2-isoprostanes during aortic endothelial cell–mediated oxidation of low density lipoprotein. FEBS Lett. 1994;348:297-300. [Medline] [Order article via Infotrieve]
27. Mullender MG, Van Der Meer DD, Huiskes R, Lips L. Osteocyte density changes in aging and osteoporosis. Bone. 1996;18:109-113. [Medline] [Order article via Infotrieve]
28. Ouchi Y, Akashita M, De Souza AC, Nakamura T, Orimo H. Age-related loss of bone mass and aortic/aortic valve calcification: reevaluation of recommended dietary allowance of calcium in the elderly. Ann N Y Acad Sci. 1993;676:297-307.[Medline] [Order article via Infotrieve]
29.
Boukhris R, Becker KL. Calcification of the
aorta and osteoporosis. JAMA. 1972;219:1307-1311.
30. Banks LM, Lees B, Macsweeney JE, Stevenson JC. Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest. 1994;24:813-817. [Medline] [Order article via Infotrieve]
31. Laroche M, Pouilles JM, Ribot C, Bendayan P, Bernard J, Boccalon H, Mazieres B. Comparison of the bone mineral content of the lower limbs in men with ischaemic atherosclerotic disease. Clin Rheumatol. 1994;13:611-614. [Medline] [Order article via Infotrieve]
32. Broulik PD, Kapitola J. Interrelations between body weight, cigarette smoking and spine mineral density in osteoporotic Czech women. Endocr Regul. 1993;27:57-60. [Medline] [Order article via Infotrieve]
33. Vukicevic S, Luyten FP, Reddi AH. Osteogenin inhibits proliferation and stimulates differentiation in mouse osteoblast-like cells (MC3T3-E1). Biochem Biophys Res Commun. 1990;166:750-756. [Medline] [Order article via Infotrieve]
34. Yohay DA, Zhang J, Thrailkill KM, Arthur JM, Quarles LD. Role of serum in the developmental expression of alkaline phosphatase in MC3T3-E1 osteoblasts. J Cell Physiol. 1994;158:467-475. [Medline] [Order article via Infotrieve]
35. Parhami F, Fang ZT, Fogelman AM, Andalibi A, Territo MC, Berliner JA. Minimally modified low density lipoprotein–induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate. J Clin Invest. 1993;92:471-478.
36.
Noda M, Vogel RL, Hasson DM, Rodan GA. Leukemia
inhibitory factor suppresses proliferation, alkaline
phosphatase activity, and type I collagen messenger ribonucleic acid
level and enhances osteopontin mRNA level in murine osteoblast-like
(MC3T3-E1) cells. Endocrinology. 1990;127:185-190.
37. Ikeda K, Matsumoto T, Morita K, Kurokawa K, Ogatta E. Inhibition of in vitro mineralization by aluminum in a clonal osteoblastlike cell line, MC3T3-E1. Calcif Tissue Int. 1986;39:319-323. [Medline] [Order article via Infotrieve]
38. Maniatopoulos C, Sodek J, Melcher AH. Bone formation in vitro by stromal cells obtained from bone marrow of young adult rats. Cell Tissue Res. 1988;254:317-330. [Medline] [Order article via Infotrieve]
39. Aubin JE, Liu F, Malaval L, Gupta AK. Osteoblast and chondroblast differentiation. Bone. 1995;17:77S-83S. [Medline] [Order article via Infotrieve]
40. Hall BK, Miyake T. The membranous skeleton: the role of cell condensations in vertebrate skeletogenesis. Anat Embryol (Berl). 1992;186:107-124. [Medline] [Order article via Infotrieve]
41. Prasad MR, Das DK. Effect of oxygen-derived free radicals and oxidants on the degradation in vitro of membrane phospholipids. Free Radic Res Commun. 1989;7:381-388. [Medline] [Order article via Infotrieve]
42. Ramseier E. Arteriosclerotic lesions of the bone arteries. Virchows Arch [A]. 1962;336:77-86.
43. Xu H, Watkins BA, Seifert MF. Vitamin E stimulates trabecular bone formation and alters epiphyseal cartilage morphometry. Calcif Tissue Int. 1995;57:293-300. [Medline] [Order article via Infotrieve]
44. Mitchell JRA, Adams JH. Aortic size and aortic calcification. Atherosclerosis. 1977;27:437-446.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  M. Mizobuchi, D. Towler, and E. Slatopolsky Vascular Calcification: The Killer of Patients with Chronic Kidney Disease J. Am. Soc. Nephrol., July 1, 2009; 20(7): 1453 - 1464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Akat, M Borggrefe, and J J Kaden Aortic valve calcification: basic science to clinical practice Heart, April 1, 2009; 95(8): 616 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Hyder, M. A. Allison, N. Wong, A. Papa, T. F. Lang, C. Sirlin, S. M. Gapstur, P. Ouyang, J. J. Carr, and M. H. Criqui Association of Coronary Artery and Aortic Calcium With Lumbar Bone Density: The MESA Abdominal Aortic Calcium Study Am. J. Epidemiol., January 15, 2009; 169(2): 186 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Terkeltaub Macrophage Glucocorticoid Receptors Join the Intercellular Dialogue in Atherosclerotic Lesion Calcification Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2096 - 2098. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Atkinson Age-related medial elastocalcinosis in arteries: mechanisms, animal models, and physiological consequences J Appl Physiol, November 1, 2008; 105(5): 1643 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mehrotra, D. Kermah, M. Budoff, I. B. Salusky, S. S. Mao, Y. L. Gao, J. Takasu, S. Adler, and K. Norris Hypovitaminosis D in Chronic Kidney Disease Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1144 - 1151. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yao, A. Shahbazian, and K. I. Bostrom Proline and {gamma}-Carboxylated Glutamate Residues in Matrix Gla Protein Are Critical for Binding of Bone Morphogenetic Protein-4 Circ. Res., May 9, 2008; 102(9): 1065 - 1074. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Chen, W. Zhang, J. Laird, S. L. Hazen, and R. G. Salomon Polyunsaturated phospholipids promote the oxidation and fragmentation of {gamma}-hydroxyalkenals: formation and reactions of oxidatively truncated ether phospholipids J. Lipid Res., April 1, 2008; 49(4): 832 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Morrisett and K. C. Vickers Vascular Calcification in Homozygote Familial Hypercholesterolemia Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 606 - 607. [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hamel, E. Abed, L. Brissette, and R. Moreau Characterization of oxidized low-density lipoprotein-induced hormesis-like effects in osteoblastic cells Am J Physiol Cell Physiol, April 1, 2008; 294(4): C1021 - C1033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Liberman, E. Bassi, M. K. Martinatti, F. C. Lario, J. Wosniak Jr, P. M.A. Pomerantzeff, and F. R.M. Laurindo Oxidant Generation Predominates Around Calcifying Foci and Enhances Progression of Aortic Valve Calcification Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 463 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Towler Vascular Calcification: A Perspective On An Imminent Disease Epidemic IBMS BoneKEy, February 1, 2008; 5(2): 41 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mohty, P. Pibarot, J.-P. Despres, C. Cote, B. Arsenault, A. Cartier, P. Cosnay, C. Couture, and P. Mathieu Association Between Plasma LDL Particle Size, Valvular Accumulation of Oxidized LDL, and Inflammation in Patients With Aortic Stenosis Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 187 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Paredes, T. Tazzeo, and L. J. Janssen E-Ring Isoprostane Augments Cholinergic Neurotransmission in Bovine Trachealis via FP Prostanoid Receptors Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 739 - 747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Al-Aly, J.-S. Shao, C.-F. Lai, E. Huang, J. Cai, A. Behrmann, S.-L. Cheng, and D. A. Towler Aortic Msx2-Wnt Calcification Cascade Is Regulated by TNF-{alpha} Dependent Signals in Diabetic Ldlr / Mice Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2589 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K Pollock, E. M Laing, C. A Baile, M. W Hamrick, D. B Hall, and R. D Lewis Is adiposity advantageous for bone strength? A peripheral quantitative computed tomography study in late adolescent females Am. J. Clinical Nutrition, November 1, 2007; 86(5): 1530 - 1538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Poulsen, P. J. Moughan, and M. C. Kruger Long-Chain Polyunsaturated Fatty Acids and the Regulation of Bone Metabolism Experimental Biology and Medicine, November 1, 2007; 232(10): 1275 - 1288. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M Weaver and S. L Mobley Calcium intake, body fat, and bones a complex relation Am. J. Clinical Nutrition, September 1, 2007; 86(3): 527 - 527. [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Huang, S. Morony, J. Lu, Z. Zhang, O. Bezouglaia, W. Tseng, S. Tetradis, L. L. Demer, and Y. Tintut Atherogenic Phospholipids Attenuate Osteogenic Signaling by BMP-2 and Parathyroid Hormone in Osteoblasts J. Biol. Chem., July 20, 2007; 282(29): 21237 - 21243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Xue, N. Comes, and T. Borras Presence of an Established Calcification Marker in Trabecular Meshwork Tissue of Glaucoma Donors Invest. Ophthalmol. Vis. Sci., July 1, 2007; 48(7): 3184 - 3194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Feng, H. Li, A. A. Rumbin, X. Wang, A. La Cava, K. Brechtelsbauer, L. W. Castellani, J. L. Witztum, A. J. Lusis, and B. P. Tsao ApoE-/-Fas-/- C57BL/6 mice: a novel murine model simultaneously exhibits lupus nephritis, atherosclerosis, and osteopenia J. Lipid Res., April 1, 2007; 48(4): 794 - 805. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Nikolov, N. Joki, T. Drueke, and Z. Massy Beyond phosphate--role of uraemic toxins in cardiovascular calcification Nephrol. Dial. Transplant., December 1, 2006; 21(12): 3354 - 3357. [Full Text] [PDF]
|
|
|
|
|
|
R. C. Johnson, J. A. Leopold, and J. Loscalzo Vascular Calcification: Pathobiological Mechanisms and Clinical Implications Circ. Res., November 10, 2006; 99(10): 1044 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Briand, P. Pibarot, J.-P. Despres, P. Voisine, J. G. Dumesnil, F. Dagenais, and P. Mathieu Metabolic Syndrome Is Associated With Faster Degeneration of Bioprosthetic Valves Circulation, July 4, 2006; 114(1_suppl): I-512 - I-517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Shao, J. Cai, and D. A. Towler Molecular Mechanisms of Vascular Calcification: Lessons Learned From The Aorta Arterioscler Thromb Vasc Biol, July 1, 2006; 26(7): 1423 - 1430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Briand, I. Lemieux, J. G. Dumesnil, P. Mathieu, A. Cartier, J.-P. Despres, M. Arsenault, J. Couet, and P. Pibarot Metabolic Syndrome Negatively Influences Disease Progression and Prognosis in Aortic Stenosis J. Am. Coll. Cardiol., June 6, 2006; 47(11): 2229 - 2236. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D E Newby, S J Cowell, and N A Boon Emerging medical treatments for aortic stenosis: statins, angiotensin converting enzyme inhibitors, or both? Heart, June 1, 2006; 92(6): 729 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Kirton, F. L. Wilkinson, A. E. Canfield, and M. Y. Alexander Dexamethasone Downregulates Calcification-Inhibitor Molecules and Accelerates Osteogenic Differentiation of Vascular Pericytes: Implications for Vascular Calcification Circ. Res., May 26, 2006; 98(10): 1264 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Hsu, S. A Venners, H. A Terwedow, Y. Feng, T. Niu, Z. Li, N. Laird, J. D Brain, S. R Cummings, M. L Bouxsein, et al. Relation of body composition, fat mass, and serum lipids to osteoporotic fractures and bone mineral density in Chinese men and women Am. J. Clinical Nutrition, January 1, 2006; 83(1): 146 - 154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Higgins, S. A. Marvel, and J. D. Morrisett Quantification of Calcification in Atherosclerotic Lesions Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1567 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Raggi, M. Davidson, T. Q. Callister, F. K. Welty, G. A. Bachmann, H. Hecht, and J. A. Rumberger Aggressive Versus Moderate Lipid-Lowering Therapy in Hypercholesterolemic Postmenopausal Women: Beyond Endorsed Lipid Lowering With EBT Scanning (BELLES) Circulation, July 26, 2005; 112(4): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Hruska, S. Mathew, and G. Saab Bone Morphogenetic Proteins in Vascular Calcification Circ. Res., July 22, 2005; 97(2): 105 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Pardo, M. J. Patel, M. C. Sykes, M. O. Platt, N. L. Boyd, G. P. Sorescu, M. Xu, J. J. W. A. van Loon, M. D. Wang, and H. Jo Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts Am J Physiol Cell Physiol, June 1, 2005; 288(6): C1211 - C1221. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Simmons, G. R. Grant, E. Manduchi, and P. F. Davies Spatial Heterogeneity of Endothelial Phenotypes Correlates With Side-Specific Vulnerability to Calcification in Normal Porcine Aortic Valves Circ. Res., April 15, 2005; 96(7): 792 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Towler Inorganic Pyrophosphate: A Paracrine Regulator of Vascular Calcification and Smooth Muscle Phenotype Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 651 - 654. [Full Text] [PDF]
|
|
|
|
|
|
B. Wu, S. Elmariah, F. S. Kaplan, G. Cheng, and E. R. Mohler III Paradoxical Effects of Statins on Aortic Valve Myofibroblasts and Osteoblasts: Implications for End-Stage Valvular Heart Disease Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 592 - 597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.E. Norman and J.T. Powell Vitamin D, Shedding Light on the Development of Disease in Peripheral Arteries Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 39 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Collin-Osdoby Regulation of Vascular Calcification by Osteoclast Regulatory Factors RANKL and Osteoprotegerin Circ. Res., November 26, 2004; 95(11): 1046 - 1057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Demer and M. Abedin Skeleton key to vascular disease J. Am. Coll. Cardiol., November 16, 2004; 44(10): 1977 - 1979. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Moe and N. X. Chen Pathophysiology of Vascular Calcification in Chronic Kidney Disease Circ. Res., September 17, 2004; 95(6): 560 - 567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Rubin and S. J. Silverberg Vascular Calcification and Osteoporosis--The Nature of the Nexus J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4243 - 4245. [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification Endocr. Rev., August 1, 2004; 25(4): 629 - 672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Soufi, M. Schoppet, A. M. Sattler, M. Herzum, B. Maisch, L. C. Hofbauer, and J. R. Schaefer Osteoprotegerin Gene Polymorphisms in Men with Coronary Artery Disease J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3764 - 3768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Yin, Q. Xu, and C. Duan Paradoxical Actions of Endogenous and Exogenous Insulin-like Growth Factor-binding Protein-5 Revealed by RNA Interference Analysis J. Biol. Chem., July 30, 2004; 279(31): 32660 - 32666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Abedin, Y. Tintut, and L. L. Demer Vascular Calcification: Mechanisms and Clinical Ramifications Arterioscler Thromb Vasc Biol, July 1, 2004; 24(7): 1161 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Vattikuti and D. A. Towler Osteogenic regulation of vascular calcification: an early perspective Am J Physiol Endocrinol Metab, May 1, 2004; 286(5): E686 - E696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tintut, S. Morony, and L. L. Demer Hyperlipidemia Promotes Osteoclastic Potential of Bone Marrow Cells Ex Vivo Arterioscler Thromb Vasc Biol, February 1, 2004; 24(2): e6 - 10. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. F. Klein, J. Allard, Z. Avnur, T. Nikolcheva, D. Rotstein, A. S. Carlos, M. Shea, R. V. Waters, J. K. Belknap, G. Peltz, et al. Regulation of Bone Mass in Mice by the Lipoxygenase Gene Alox15 Science, January 9, 2004; 303(5655): 229 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Demer and Y. Tintut Mineral Exploration: Search for the Mechanism of Vascular Calcification and Beyond: The 2003 Jeffrey M. Hoeg Award Lecture Arterioscler Thromb Vasc Biol, October 1, 2003; 23(10): 1739 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-L. Chan Is aortic stenosis a preventable disease? J. Am. Coll. Cardiol., August 20, 2003; 42(4): 593 - 599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Jian, N. Narula, Q.-y. Li, E. R. Mohler III, and R. J. Levy Progression of aortic valve stenosis: TGF-{beta}1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis Ann. Thorac. Surg., February 1, 2003; 75(2): 457 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Proudfoot, J.D. Davies, J.N. Skepper, P.L. Weissberg, and C.M. Shanahan Acetylated Low-Density Lipoprotein Stimulates Human Vascular Smooth Muscle Cell Calcification by Promoting Osteoblastic Differentiation and Inhibiting Phagocytosis Circulation, December 10, 2002; 106(24): 3044 - 3050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sun, H. Unoki, X. Wang, J. Liang, T. Ichikawa, Y. Arai, M. Shiomi, S. M. Marcovina, T. Watanabe, and J. Fan Lipoprotein(a) Enhances Advanced Atherosclerosis and Vascular Calcification in WHHL Transgenic Rabbits Expressing Human Apolipoprotein(a) J. Biol. Chem., November 27, 2002; 277(49): 47486 - 47492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Parhami, B. Basseri, J. Hwang, Y. Tintut, and L. L. Demer High-Density Lipoprotein Regulates Calcification of Vascular Cells Circ. Res., October 4, 2002; 91(7): 570 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Mohler III Vascular calcification: good, bad or ugly? Vascular Medicine, August 1, 2002; 7(3): 161 - 162. [PDF]
|
|
|
|
 |
|
 L. L Demer Vascular calcification and osteoporosis: inflammatory responses to oxidized lipids Int. J. Epidemiol., August 1, 2002; 31(4): 737 - 741. [Full Text] [PDF]
|
|
|
|
|
|
N. M. Rajamannan, M. Subramaniam, M. Springett, T. C. Sebo, M. Niekrasz, J. P. McConnell, R. J. Singh, N. J. Stone, R. O. Bonow, and T. C. Spelsberg Atorvastatin Inhibits Hypercholesterolemia-Induced Cellular Proliferation and Bone Matrix Production in the Rabbit Aortic Valve Circulation, June 4, 2002; 105(22): 2660 - 2665. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tintut, F. Parhami, A. Tsingotjidou, S. Tetradis, M. Territo, and L. L. Demer 8-Isoprostaglandin E2 Enhances Receptor-activated NFkappa B Ligand (RANKL)-dependent Osteoclastic Potential of Marrow Hematopoietic Precursors via the cAMP Pathway J. Biol. Chem., April 12, 2002; 277(16): 14221 - 14226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Demer Adipose Rex: Fat and Fats That Rule Differentiation Circ. Res., February 22, 2002; 90(3): 241 - 243. [Full Text] [PDF]
|
|
|
|
|
|
Y. Tintut, J. Patel, M. Territo, T. Saini, F. Parhami, and L. L. Demer Monocyte/Macrophage Regulation of Vascular Calcification In Vitro Circulation, February 5, 2002; 105(5): 650 - 655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Demer Cholesterol in Vascular and Valvular Calcification Circulation, October 16, 2001; 104(16): 1881 - 1883. [Full Text] [PDF]
|
|
|
|
|
|
L. L. Demer Boning Up (or Down) on Statins Arterioscler Thromb Vasc Biol, October 1, 2001; 21(10): 1565 - 1566. [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Janssen Isoprostanes: an overview and putative roles in pulmonary pathophysiology Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1067 - L1082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. DRAKE, E. SCHADT, K. HANNANI, J. M. KABO, K. KRASS, V. COLINAYO, L. E. GREASER III, J. GOLDIN, and A. J. LUSIS Genetic loci determining bone density in mice with diet-induced atherosclerosis Physiol Genomics, April 27, 2001; 5(4): 205 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. S. Browner, L.-Y. Lui, and S. R. Cummings Associations of Serum Osteoprotegerin Levels with Diabetes, Stroke, Bone Density, Fractures, and Mortality in Elderly Women J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 631 - 637. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Tintut, J. Patel, F. Parhami, and L. L. Demer Tumor Necrosis Factor-{alpha} Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway Circulation, November 21, 2000; 102(21): 2636 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Parhami, A. Garfinkel, and L. L. Demer Role of Lipids in Osteoporosis Arterioscler Thromb Vasc Biol, November 1, 2000; 20(11): 2346 - 2348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Hak, H. A. P. Pols, A. M. van Hemert, A. Hofman, and J. C. M. Witteman Progression of Aortic Calcification Is Associated With Metacarpal Bone Loss During Menopause : A Population-Based Longitudinal Study Arterioscler Thromb Vasc Biol, August 1, 2000; 20(8): 1926 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. F. Redberg, N. Rifai, L. Gee, and P. M. Ridker Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening J. Am. Coll. Cardiol., July 1, 2000; 36(1): 39 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Nishino, M. J. Malloy, J. Naya-Vigne, J. Russell, J. P. Kane, and R. F. Redberg Lack of association of lipoprotein(a) levels with coronary calcium deposits in asymptomatic postmenopausal women J. Am. Coll. Cardiol., February 1, 2000; 35(2): 314 - 320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tintut, F. Parhami, V. Le, G. Karsenty, and L. L. Demer Inhibition of Osteoblast-specific Transcription Factor Cbfa1 by the cAMP Pathway in Osteoblastic Cells. UBIQUITIN/PROTEASOME-DEPENDENT REGULATION J. Biol. Chem., October 8, 1999; 274(41): 28875 - 28879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Wada, M. D. McKee, S. Steitz, and C. M. Giachelli Calcification of Vascular Smooth Muscle Cell Cultures : Inhibition by Osteopontin Circ. Res., February 5, 1999; 84(2): 166 - 178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bucay, I. Sarosi, C. R. Dunstan, S. Morony, J. Tarpley, C. Capparelli, S. Scully, H. L. Tan, W. Xu, D. L. Lacey, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification Genes & Dev., May 1, 1998; 12(9): 1260 - 1268. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Tintut, F. Parhami, K. Bostrom, S. M. Jackson, and L. L. Demer cAMP Stimulates Osteoblast-like Differentiation of Calcifying Vascular Cells. POTENTIAL SIGNALING PATHWAY FOR VASCULAR CALCIFICATION J. Biol. Chem., March 27, 1998; 273(13): 7547 - 7553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jono, C. Peinado, and C. M. Giachelli Phosphorylation of Osteopontin Is Required for Inhibition of Vascular Smooth Muscle Cell Calcification J. Biol. Chem., June 23, 2000; 275(26): 20197 - 20203. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Parhami, Y. Tintut, A. Ballard, A. M. Fogelman, and L. L. Demer Leptin Enhances the Calcification of Vascular Cells : Artery Wall as a Target of Leptin Circ. Res., May 11, 2001; 88(9): 954 - 960. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||