© 1995 American Heart Association, Inc.
Articles |
Early Change of Vascular Permeability in Hypercholesterolemic Rabbits
From the Departments of Internal Medicine (Cardiology) and Ophthalmology (S-W.C., M-S.C.), National Taiwan University Hospital, Taipei, Taiwan, ROC.
Correspondence to Dr Yuan-Teh Lee, Department of Internal Medicine (Cardiology), National Taiwan University Hospital, 7 Chung-Shan S Rd, Taipei, Taiwan, ROC, 10016.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Abstract To study the effect of hyperlipidemia on vascular permeability, serial anterior chamber fluorophotometric examinations were carried out on 33 control rabbits (group 1) and 32 diet-induced hypercholesterolemic (group 2) rabbits. Changes in the blood-aqueous barrier function associated with total serum cholesterol (CHO) and triglyceride (TG) levels were studied at the beginning of the study and every 2 weeks thereafter for up to 16 weeks following 0.5% cholesterol–enriched diet feeding. Concurrently, a slit-lamp biomicroscope was used to examine the iris for evidence of atheromatous plaque. In group 1, the CHO level decreased slightly during the first 6 weeks and remained rather steady thereafter. The status of the blood-aqueous barrier correlated significantly with serum CHO and TG levels (r=.46, P<.001; r=.23, P=.01, respectively). In group 2, CHO and TG levels increased significantly after 2 and 8 weeks of cholesterol-enriched diet feeding, respectively. The blood-aqueous barrier also became more permeable than that in group 1 after 2 weeks' and increased above its baseline level after 6 weeks' feeding. Both CHO and TG levels correlated well with the degree of blood-aqueous barrier breakdown (r=.51, P<.001; r=.25, P<.001, respectively). The first evidence of iridic lipid-streak deposition was noted at 7.6±0.7 weeks, while definite iridic atheromatous plaque appeared 11.2±0.7 weeks after feeding. The change in the blood-aqueous barrier also correlated well with the semiquantitative score of iridic plaque (r=.58, P<.001) and usually preceded visual evidence of plaque formation. Pathological examinations of the eye showed marked foam cell infiltration in the stroma of the ciliary body, the ciliary process, and iris stroma, similar to changes in atheromas of the thoracic aorta after 16 weeks of feeding. In conclusion, anterior segment fluorophotometry is a valuable tool for detecting vascular integrity in vivo. These results suggest that the permeability change correlates well with serum CHO level and occurs in the very early stages of atherogenesis.
Key Words: vascular permeability • fluorophotometer • hyperlipidemia • blood-aqueous barrier • iris
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The vascular endothelium forms a highly selective permeability barrier.1 2 3 Endothelial cells normally attach to each other by tight and gap junctions, which may serve as potential sites of increased endothelial transport, particularly when they have been injured in diseases such as atherosclerosis or hypertension. Hypercholesterolemia is closely related to atherosclerosis and is one of the most important coronary risk factors.4 Besides smooth muscle cell proliferation and accumulation of connective tissue matrix, changes in endothelial permeability are major common pathogenic mechanisms in atherosclerosis. Several studies have pointed out that hypercholesterolemia enhances vascular endothelial dysfunction,5 6 smooth muscle cell proliferation,7 blood coagulability, and thrombogenicity.8 9 In diet-induced hypercholesterolemic rabbits, a prominent site for the development of xanthomata is the eye, in which the capacity of the iris to accumulate cholesterol is particularly noteworthy.10 Because vascular lesions in rabbits with experimental atherosclerosis are similar to native atherosclerosis in humans and because there is a high correlation between the severity of iridic and aortic involvement in experimental models,10 changes in iridic vessels in the eye will be good indicators of the general status of the vascular system.
The blood-aqueous barrier can be evaluated clinically by anterior segment fluorescein angiography,11 12 13 the cell-flare meter,14 and fluorophotometry.15 16 Among these, fluorophotometry is the most sensitive method to quantify the breakdown of the blood-aqueous barrier.17 Because of corneal clarity, the iris vasculature is one of the most easily assessed vessels in the body. This anterior chamber fluorophotometric study on detecting early changes in vascular permeability provides a good "window" for monitoring the pathological or pharmacological effects of various factors on systemic arterioles. In this experiment, we used fluorophotometry to detect the status of the blood-aqueous barrier in hyperlipidemic rabbits.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Animals, Diets, and Examination Schedules
Male New Zealand White rabbits weighing 1.4 to 1.6 kg were randomly divided into two groups. Thirty-three animals fed standard rabbit chow (Purina 5321) for 4 months served as controls (group 1). Another 32 animals (group 2) were fed the same diet enriched with 0.5% cholesterol (Wako Co) and coconut oil (Yeali Co). The lipids made up 40% of the total energy source of the diet. Both the salt and vitamin mixtures met American Institute of Nutrition Standards. All animals were allowed food and water ad libitum during the experiment, except for an overnight fast before blood sampling.
Biochemical Measurements
Blood was sampled at the time of fluorophotometric
examination. Serum total cholesterol (CHO) and triglyceride (TG) levels
were determined by automated enzymatic methods (Merck 14366 and 14354,
respectively).18 19
Fluorophotometry
Anterior chamber fluorophotometry was done at the beginning and
then every 2 weeks for up to 16 weeks of the feeding schedule. Anterior
chamber fluorophotometry was performed according to a protocol modified
from that suggested by Miyake et al20 and Fearnley et
al.21 The rabbits were anesthetized with an intramuscular
injection of a 2:3 (vol/vol) mixture of xylazine (2%, Bayer) and
ketamine (50 mg/mL, Parke-Davis Co). Fluorophotometry was performed
with the Fluorotron Master II (Coherent Co) fitted with an optical
anterior segment adapter. After measurement of the lens and corneal
autofluorescence, each rabbit received an intravenous injection of 10%
fluorescein sodium (15 mg per 1 kg body weight). Because
autofluorescence of the rabbit cornea and lens was small, there was
hardly a significant spread between the lens and corneal
autofluorescence peaks. Anterior chamber fluorescein concentration 60
minutes after intravenous injection of sodium fluorescein was measured.
The mean value of anterior chamber fluorescence along the visual axis
over a 2.0-mm band positioned in the anterior chamber was averaged
(F60). We used F60 to represent the status of the blood-aqueous
barrier.16 20 Because it is impossible to distinguish
between the various metabolites of fluorescein with the Fluorotron
Master, all fluorophotometric results were expressed as total
fluorescence in terms of equivalent concentrations of fluorescein
sodium.
Morphology
The iridic plaque was initially a yellowish streak-like deposit
on the iris. In the advanced stage, the atheroma protruded into the
posterior chamber from the posterior aspect of the iris. Two
independent observers examined both eyes of each animal for the
presence of iridic atheroma during fluorophotometric examinations. When
no iridic atheroma was detected by visual inspection, we used a
slit-lamp biomicroscope to determine whether there was any lipid streak
deposit. The iridic atheromatous plaques (IAPs) were scored as follows:
0, no evidence of atheromatous plaque, even with the slit-lamp
biomicroscope; 1, streak-like deposits detected under the slit-lamp
biomicroscope but not detectable by visual inspection; and 2, iridic
plaque visible by both slit-lamp biomicroscope and visual inspection.
The times at which the first evidence of iridic deposition appeared,
both with and without biomicroscopic aid, were recorded. All animals
were killed by an overdose of intravenous pentobarbital at the end of
the 16-week experiment period. Both eyes of each animal were enucleated
immediately. They were processed for hematoxylin and eosin (H&E) stain
and examined under a light microscope. A segment of the thoracic aorta
containing atheromatous plaque was also dissected and processed for H&E
stain.
Data Analysis
All values are expressed as mean±SEM. The levels of CHO and TG,
the IAP score, and F60 in each group were averaged at different
intervals. To avoid overestimation, data for both eyes of each animal
were averaged and analyzed. Chronological changes in F60, CHO, TG, and
IAP score were examined by one-way ANOVA in both groups. Differences
between the two groups at the various experimental intervals were
examined by Student's t test. Correlations of CHO, TG, and
IAP score to F60 were examined. A probability value of <.05 was
considered statistically significant. The time at which IAP appeared,
identified with or without biomicroscopic aid, was averaged.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The Table
summarizes the chronological changes of
CHO, F60, and IAP score.
|
Blood Chemistry
In group 2, the CHO level escalated rather rapidly in the first 2
months. This increase was significant after 2 weeks on a
cholesterol-enriched diet. However, it became less acute in the third
month, even declined from 12 to 14 weeks, and escalated again from 14
to 16 weeks. The TG level also increased significantly after 8 weeks of
a cholesterol-enriched diet. In contrast, there was a slight decrease
in CHO and TG levels in the first 6 weeks; these levels remained rather
steady thereafter in group 1. The CHO correlated significantly with the
TG level in both groups (r=.35, P<.001;
r=.57, P<.001, respectively).
Fluorophotometry
Fig 1 shows the chronological changes of F60,
CHO, and TG in both groups. In group 1, both CHO and TG levels
correlated with F60 (r=.46, P<.001;
r=.23, P=.01, respectively). The F60 in the first
few weeks decreased slightly, in accordance with the slight decrease in
CHO, and remained rather steady thereafter. In group 2, there was no
initial decrease in F60. Instead, it remained rather stable initially
and increased above its baseline level after the first 6 weeks of
feeding. It also escalated further up to 16 weeks. However, there was a
slight drop of F60 from 10 to 14 weeks, at which time the CHO levels
also dropped. The rise in F60 roughly paralleled the rise in CHO and TG
(r=.51, P<.001; r=.25,
P<.001, respectively). F60 always correlated better with
CHO than with TG levels in both groups. There was a significant
difference in F60 between groups 1 and 2 after 2 weeks of a
cholesterol-enriched diet (group 1: 497.9±15.4 ng/mL; group 2:
608.1±28.1 ng/mL, P<.001).
|
indicates F60 in group 1;
, F60 in group 2; 
, CHO in group 1; 
, CHO in group 2;
, TG in group 1; and 
, TG in group 2.
Morphology
With the aid of a slit-lamp biomicroscope, the first trace
of iridic streak deposition appeared at 7.6±0.7 weeks, while definite
IAP could be identified without biomicroscopic aid at 11.2±0.7 weeks
of a cholesterol-enriched diet. The Table
also summarizes mean IAP
score at different time points in group 2. IAP score increased most
significantly in the third and fourth months. Both CHO and F60
correlated significantly with IAP score (r=.45,
P=.002; r=.58, P<.001, respectively).
Pathological examinations at the end of the 16-week experiment showed
there were abundant foam cells in the irides (Fig 2,
top), ciliary bodies, ciliary processes (Fig 2, middle),
and choroid of group 2 animals but not in those of group 1. The
trabecular meshwork was also infiltrated by foam cells in some cases
(Fig 2, bottom). These changes were similar to the atheromatous plaques
of aortas (Fig 3). The conjunctiva, lens, and retinas
seemed little affected by the systemic hypercholesterolemia.
|
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Although the posterior fourth of the iris is derived from the neuroectoderm, the anterior three fourths, ie, the vascular stroma, is mesodermal and thus similar to systemic arterioles. The iridic vessels, which frequently appear thick-walled, consist of an endothelial lining and a thick collar of collagen fibrils. This thick adventitia accounts for the remarkably low permeability of iridic vessels in the normal state.22 The capillaries in the iris have no fenestration, and the adjacent endothelial cells attach to each other by junctional complexes.23 Normally, these intercellular attachments allow little extravascular permeation, even to small molecules such as fluorescein,24 and thus form a blood-aqueous barrier. The aqueous fluid is in part a filtrate of serum. The huge molecular size of low-density (cholesterol-rich) serum lipoprotein probably prevents it from gaining easy access to the aqueous. Therefore, in diet-induced hypercholesterolemic rabbit models, the aqueous fluid might show only a modest increase in cholesterol despite an enormous change in serum cholesterol level.25 However, this small increase in cholesterol in the aqueous does not guarantee an intact blood-aqueous barrier. During the early stages of experimental hyperlipidemia in hamsters, the aortic wall shows increased permeability to albumin.26 In this study, we demonstrated an increase in iridic vessel permeability to sodium fluorescein in the early stage of diet-induced hyperlipidemia, even before visual evidence of iridic atheromatous plaque formation. Furthermore, F60 correlated well with both CHO level and IAP score. Because vascular lesions in rabbits with experimental atherosclerosis are similar to native atherosclerosis in humans, we believe that disruption of the integrity of the iridic vessel wall is a good indicator of incompetence of the systemic vasculature.
In group 1, the initial decrease in F60 may have been due to the concurrent decrease of CHO level or to the age-associated functional change in iridic vascular permeability. F60 became significantly different between groups 1 and 2 only after 2 weeks on a cholesterol-enriched diet because there was no initial decrease in both CHO and F60 levels in group 2. However, while the CHO level rose significantly after 2 weeks, F60 increased above its baseline level only after 6 weeks in group 2. These results demonstrated that although it lagged slightly behind, the trend in F60 roughly paralleled the change in CHO in both groups. We do not know the exact mechanism by which lipid levels modified F60. Nevertheless, a high-fat, high-cholesterol diet may cause endothelial injury6 and alter the endothelial barrier. It has been postulated that alterations in permeability of the local vasculature lead to changes in the iridic deposits,27 28 which lead to the development of sudanophilic substance accumulation and foam cell formation.27 29 30 In the study of Roscoe and Vogel,10 in which rabbits were fed 1% cholesterol, there was a linear increase in total iridic cholesterol during the first 2 months of cholesterol feeding. Nevertheless, the biggest increase in total iridic cholesterol was in the third month. In our study, the F60 and serum total CHO levels reached a peak in weeks 10 to 12 and a trough in week 14 and then rose again. Roscoe and Vogel did not describe the chronological changes in serum CHO and TG in their results, while we found a rather rapid increase in serum CHO in the first 2 months. F60 increased slightly in the first month and rose more rapidly in the second and third months, in a delayed pattern similar to the increase in serum total CHO level. However, the IAP score increased most notably in the third and fourth months. Although F60 also correlated well with the IAP score, the alteration in F60 usually preceded visual evidence of iridic deposits, which were already visible under a slit-lamp biomicroscope after 7.6±0.7 weeks' feeding of a cholesterol-enriched diet.
After reaching a peak in weeks 10 to 12, both F60 and CHO had a slight drop and a trough in week 14. The fact that the rabbits ate less and their body weights also decreased slightly during this period might partially explain the decrease in both serum total CHO and F60. Another possibility is that thrombosis might have occurred in the iridic arterioles, because hyperlipidemia would alter the platelet surface negative charge31 and enhance platelet–vessel wall interactions.32 Both factors might contribute to acute thrombosis formation, which could have resulted in less inflow of fluorescein-rich serum. Therefore, F60 was smaller in some rabbits, although we presumed that there would be a more significant breakdown of the blood-aqueous barrier. At week 16, the more severely broken-down blood-aqueous barrier contributed to an even higher F60, with more advanced hyperlipidemia, despite the possibility of vascular thrombosis.
In this study, we do not know whether breakdown of the blood-aqueous barrier involved the iridic arterioles or capillaries. However, a previous histopathologic examination delineated that the first evidence of an iridic lesion was the presence of lipid droplets in the walls of small blood vessels.30 Lipid droplets or globules then appeared in the adjacent connective tissue. Both conditions preceded the appearance of lipid-filled macrophage or foam cells,30 similar to the atheromas found in systemic atherosclerosis. This might reflect a change in the vascular permeability during the early stages of an increased serum cholesterol level.29 Because the animals were killed after being fed a cholesterol-enriched diet for 16 weeks, histopathologic changes in the early stages were not reproduced. However, we found abundant foam cell infiltration that was similar to advanced atheroma formation reported in the literature.10,30 The iris connective tissue has little effect on the passage of the fluorescein molecule once it has entered the subendothelial space. Thus, the anterior chamber fluorescein concentration would increase with subtle changes of the blood-aqueous barrier, possibly long before the visually detectable iridic deposition or pathologically detectable sudanophilic substance accumulation.
In summary, using anterior segment fluorophotometry, we evaluated vascular endothelial integrity in vivo. The change in vascular permeability correlated well with serum CHO level and occurred during the very early stages of atherosclerosis. Moreover, this alteration of vascular permeability preceded visual evidence of atheromatous plaque. This method was found to provide a good window into the early detection of endothelial functional change in systemic hypercholesterolemia and possibly atherosclerosis.
|
Acknowledgments |
|---|
This work was supported by research grant DOH83-HR-301 from the Department of Health, Executive Yuan of Taiwan, ROC.
Received October 30, 1994; accepted January 20, 1995.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Simionescu N, Simionescu M, Palade GE. Permeability of muscle capillaries to small heme-peptides: evidence for the existence of patent transendothelial channels. J Cell Biol. 1975;64:586-607.
2. Huttner I, Boutet M, More RH. Studies on protein passage through arterial endothelium, I: structural correlated of permeability in rat arterial endothelium. Lab Invest. 1973;28:672-677. [Medline] [Order article via Infotrieve]
3.
Renkin EM. Multiple pathways of capillary permeability.
Circ Res. 1977;41:735-743.
4. Simons LA. Interrelations of lipids and lipoproteins with coronary artery disease mortality in 19 countries. Am J Cardiol. 1986;57:5G-10G. [Medline] [Order article via Infotrieve]
5. Ross R, Glomset JA. The pathogenesis of atherosclerosis. N Engl J Med. 1976;295:369-377. [Medline] [Order article via Infotrieve]
6.
Ross R, Harker L. Hyperlipidemia and atherosclerosis.
Science. 1976;193:1094-1100.
7. Wissler RW, Vesselinovitch D, Getz GJ. Abnormalities of the arterial wall and its metabolism in atherogenesis. Prog Cardiovasc Dis. 1976;18:341-369. [Medline] [Order article via Infotrieve]
8.
Golino P, Maroko PR, Carew TE. Efficacy of platelet
depletion in counteracting the detrimental effect of acute
hypercholesterolemia on infarct size and the no-reflow phenomenon in
rabbits undergoing coronary artery occlusion-reperfusion.
Circulation. 1987;76:173-180.
9. Shattil SS, Anay-Galindo R, Bennett B, Colman RW, Cooper RA. Platelet hypersensitivity induced by cholesterol incorporation. J Clin Invest. 1975;55:636-643.
10.
Roscoe HG, Vogel AW. Lipid changes in the eye concomitant with
the development of atherosclerosis in the aorta in the rabbit.
Circ Res. 1968;23:633-643.
11. Kottow MH, Hendrickson P. Iris angiography in cystoid macular edema after cataract extraction. Arch Ophthalmol. 1975;61:487-493.
12.
Easty D, Dallas N, O'Malley R. Aphakic macular oedema
following prosthetic lens implantation. Br J Ophthalmol. 1977;61:321-326.
13. Miyake K. Prevention of cystoid macular edema after lens extraction by topical indomethacin, II: a control study in bilateral extraction. Jpn J Ophthalmol. 1978;22:80-94.
14. Sawa M, Tsurimaki Y, Tsuru T, Shimizu H. New quantitative method to determine protein concentration and cell number in aqueous in vivo. Jpn J Ophthalmol. 1988;32:132-142. [Medline] [Order article via Infotrieve]
15. Araie M, Sawa M, Takase M. Effect of topical indomethacin on the blood-aqueous barrier after intracapsular extraction of senile cataract: a fluorophotometric study. Jpn J Ophthalmol. 1981;25:237-247.
16.
Sanders DR, Kraff MC, Lieberman HL, Peyman GA, Tarabishy S.
Breakdown and reestablishment of the blood-aqueous barrier with implant
surgery. Arch Ophthalmol. 1982;100:588-590.
17. Maurice DM. A new objective fluorophotometer. Exp Eye Res. 1963;2:33-38. [Medline] [Order article via Infotrieve]
18. Allain LA, Poon LS, Chan LSG, Richmond W, Fu PL. Enzymatic determination of total serum cholesterol. Clin Chem. 1974;20:470-475. [Abstract]
19.
McGown MW, Artiss JD, Strandbergh DR, Zak B. A
peroxidase-coupled method for the colorimetric determination of serum
triglycerides. Clin Chem. 1983;29:538-542.
20.
Miyake K, Asakura M, Maekubo K. Consensual reactions of human
blood-aqueous barrier to implant operations. Arch
Ophthalmol. 1984;102:558-561.
21.
Fearnly IR, Spalton DJ, Smith SE. Anterior segment
fluorophotometry in acute anterior uveitis. Arch
Ophthalmol. 1987;105:1550-1555.
22. Hogan MJ, Zimmermann LE. The uveal tract. In: Ophthalmic Pathology: An Atlas and Textbook. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1962:344-468.
23. Hogan MJ, Alvarado IA, Weddell JE. Iris and anterior chamber. In: Histology of the Human Eye: An Atlas and Textbook. Philadelphia, Pa: WB Saunders Co; 1971:202-259.
24. McMahon RT, Tso MOM, McLean IW. The histologic localization of sodium fluorescein in human ocular tissues. Am J Ophthalmol. 1975;80:1058-1065. [Medline] [Order article via Infotrieve]
25. Rubenstein RA, Whereat AF, Nanarian I. Effect of hypercholesterolemia on the eye and on aortic transplants in the anterior chamber. Am J Ophthalmol. 1967;63:972-978. [Medline] [Order article via Infotrieve]
26. Georgescu L, Antohe F, Simionescu N. The permeability of aortic endothelium to 125I-BSA in hyperlipidemic hamster: effect of histamine and serotonin. Physiologie. 1986;23:221-225. [Medline] [Order article via Infotrieve]
27.
Cogan DG, Kuwabara T. Ocular changes in experimental
hypercholesterolemia. Arch Ophthalmol. 1959;61:219-225.
28. Friedman M, Byers SO. Some local factors affecting iridic lipid infiltration in hypercholesterolemic rabbits. Am J Physiol. 1959;197:842-846.
29. Ross R. Factors influencing atherogenesis. In: Schlant RC, Alexander RW, eds. The Heart: Arteries and Veins. 8th ed. New York, NY: McGraw-Hill Publishing Co; 1994:989-1008.
30. Janes RG. Changes in rabbit's eye caused by cholesterol feeding. Am J Ophthalmol. 1964;58:819-828. [Medline] [Order article via Infotrieve]
31. Lupu C, Calb M, for the Institute of Cellular Biology and Pathology, Bucharest, Romania. Changes in the platelet surface charge in rabbits with experimental hypercholesterolemia. Atherosclerosis. 1988;72:77-82. [Medline] [Order article via Infotrieve]
32.
Badimon JJ, Badimon L, Turitto VT, Fuster V. Platelet
deposition at high shear rates is enhanced by high plasma cholesterol
levels: in vivo study in the rabbit model.
Arterioscler Thromb. 1991;11:395-402.
This article has been cited by other articles:
 |
|
 |
|
  H.-I Yeh, C.-S. Lu, Y.-J. Wu, C.-C. Chen, R.-C. Hong, Y.-S. Ko, M.-S. Shiao, N. J. Severs, and C.-H. Tsai Reduced Expression of Endothelial Connexin37 and Connexin40 in Hyperlipidemic Mice: Recovery of Connexin37 After 7-Day Simvastatin Treatment Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1391 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Rodriguez-Porcel, A. Lerman, J. Herrmann, R. S. Schwartz, T. Sawamura, M. Condorelli, C. Napoli, and L. O. Lerman Hypertension exacerbates the effect of hypercholesterolemia on the myocardial microvasculature Cardiovasc Res, April 1, 2003; 58(1): 213 - 221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. O. Bonetti, S. H. Wilson, M. Rodriguez-Porcel, D. R. Holmes Jr, L. O. Lerman, and A. Lerman Simvastatin preserves myocardial perfusion and coronary microvascular permeability in experimental hypercholesterolemia independent of lipid lowering J. Am. Coll. Cardiol., August 7, 2002; 40(3): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rodriguez-Porcel, A. Lerman, P. J. M. Best, J. D. Krier, C. Napoli, and L. O. Lerman Hypercholesterolemia impairs myocardial perfusion and permeability: role of oxidative stress and endogenous scavenging activity J. Am. Coll. Cardiol., February 1, 2001; 37(2): 608 - 615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tsimikas, B. P. Shortal, J. L. Witztum, and W. Palinski In Vivo Uptake of Radiolabeled MDA2, an Oxidation-Specific Monoclonal Antibody, Provides an Accurate Measure of Atherosclerotic Lesions Rich in Oxidized LDL and Is Highly Sensitive to Their Regression Arterioscler. Thromb. Vasc. Biol., March 1, 2000; 20(3): 689 - 697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Rutledge, M. M. Woo, A. A. Rezai, L. K. Curtiss, and I. J. Goldberg Lipoprotein Lipase Increases Lipoprotein Binding to the Artery Wall and Increases Endothelial Layer Permeability by Formation of Lipolysis Products Circ. Res., June 19, 1997; 80(6): 819 - 828. [Abstract] [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||