© 1999 American Heart Association, Inc.
Brief Review |
Apoptosis
Basic Concepts and Implications in Coronary Artery Disease
From the Department of Internal Medicine and Cardiovascular Diseases (P.J.M.B., D.H., G.S., R.S.S., D.R.H., Jr, A.L.) and the Department of Biochemistry and Molecular Biology (R.D.S.), Mayo Clinic and Mayo Foundation, Rochester, Minn.
Correspondence to Amir Lerman, MD, Department of Internal Medicine and Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, MN 55905. E-mail lerman.amir{at}mayo.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
Abstract—Apoptosis is an active form of cell death that is intricately regulated and distinct from necrosis. Data suggest that apoptosis may play a role in the pathophysiology of coronary atherosclerotic disease. Anatomic evidence of apoptosis has been observed in coronary atherosclerosis, restenosis, and transplant arteriopathy, accompanied by an increase in biochemical and genetic markers of apoptosis. Vasoactive substances such as nitric oxide and angiotensin II also regulate vascular smooth muscle cell apoptosis; vasodilating factors may induce apoptosis, whereas vasoconstricting factors may inhibit apoptosis. The aim of this article is to review key points regarding the detection of apoptosis, its regulation, and its possible role in the pathogenesis of coronary artery disease.
Key Words: apoptosis • cell death • atherosclerosis • restenosis • coronary disease
|
Introduction |
|---|
|
TopAbstractIntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
In the past 3 decades, 2 distinct forms of cell death, necrosis and apoptosis, have been defined in terms of mechanism, sequence of events, biochemistry, and morphology. Necrosis refers to a range of morphological changes resulting from the enzymatic digestion of the cell, the disruption of cellular membranes, and the denaturing of proteins that accompanies cell death. Apoptosis, in contrast, is a programmed, active, highly selective mechanism of cell death allowing for the removal of cells that are redundant or excessively damaged.1 Apoptosis is initiated by a number of different stimuli, including DNA damage, intracellular damage, toxins, and extracellular signals.2 3 4 In multicellular organisms apoptosis is an essential component of development and cellular regulation.5 6 Abnormal regulation of apoptosis can lead to disorders such as cancer, lymphocyte depletion in AIDS, and atrophy or degeneration of tissues.7 8 Apoptosis in both excessive and reduced amounts has pathological implications. Thus, control of the apoptotic mechanism may have significant therapeutic implications.
In the cardiovascular system, apoptosis has been recently found in association with ischemic and idiopathic dilated cardiomyopathies, myocardial cell death after infarction, arrhythmogenic right ventricular dysplasia, long-QT syndrome, and other conduction system disorders.9 10 11 12 13 Apoptosis has also been implicated as a prominent feature in coronary artery disease associated with advanced atherosclerosis and transplant arteriopathy.14 15 16 These finding are supported by evidence of the increased expression of molecular markers of apoptosis in atherosclerotic tissue.14 16 17 Additionally, vasoactive mediators that are altered in atherosclerosis, such as nitric oxide, endothelin, and angiotensin II, regulate vascular smooth muscle and endothelial cell apoptosis.18 19 20 21 Furthermore, inhibition of endothelin-1 by endothelin receptor antagonists increases apoptosis.22 The exact role of apoptosis in the pathophysiology of coronary disease is as yet unknown, but the association of the cardiovascular risk factors, hypertension and hypercholesterolemia, with increased apoptosis suggests that apoptosis may play a role in the pathophysiology of atherosclerosis. Additionally, apoptosis has been implicated in the pathophysiology of syndromes that develop from coronary atherosclerosis, including myocardial infarctions and heart failure. The exact understanding of cellular growth and apoptosis in these disorders will likely further our understanding and ability to regulate the progression of these diseases.
|
Methods to Detect Apoptosis |
|---|
|
TopAbstractIntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
Detection of apoptosis is challenging owing to the dynamic nature of the process. First, apoptosis and removal of the cellular debris can be completed in just a few hours and therefore, the evidence of apoptosis may go undetected, depending on the sampling time. This may lead to the false conclusion that apoptosis does not occur and thus does not contribute to the pathogenesis of a disease. Moreover, there are technical limitations in the currently applied methods for detecting apoptosis.
Morphology
In 1965, Kerr first described the 2 distinct morphological
types of cell death, apoptosis and necrosis, based on
histochemical changes in the lysosomes of ischemic
hepatic tissue (see Table 1
).23 When the
cells died via apoptosis they had unique morphological
features, typically without associated inflammation; this type of cell
death continued over weeks after the insult.1
Morphology continues to be an important method for the detection of
apoptosis. Although light microscopy alone can often detect the
features of apoptosis, electron microscopy is often used owing
to its improved reliability (see Figure 1). Electron microscopy is essential when
evaluating cells with a high nucleus-to-cytoplasm ratio because of the
difficulty in distinguishing necrosis from apoptosis in these
cells.24 Morphologically, when a cell undergoes
apoptosis, the cell shrinks and the chromatin becomes pyknotic
and condensed into sharply delineated masses present at the edge of
the nuclear envelope. Simultaneously with these changes,
cell volume decreases, cytoplasmic organelles compact, and cell density
increases. Microvilli disappear, cytoplasmic blebs form at the cell
surface, and then portions of the cell bud to create apoptotic
bodies. These apoptotic bodies, or the remainder of the
apoptotic cells, may be phagocytized or may remain free and
undergo disruption by secondary necrosis.24 In
this circumstance, apoptosis may be associated with
inflammation. The maintenance of the integrity of the cell
membrane is quite distinct from necrosis and is essential to prevent
the promotion of inflammation. Although inflammation is not typically
present, mononuclear cells may be present in tissues where
apoptosis is being induced.25
Morphological evaluation for apoptosis may also be confounded
by the occasional confusion of apoptotic bodies with
autophagocytic vacuoles.
|
|
In addition to light microscopy and electron microscopy for the
morphological evaluation of apoptosis, confocal laser scanning
microscopy has become an important adjunct in evaluating nuclear
chromatin morphology (see Figure 2). To
determine the presence of cell death, this technique uses a
fluorescent DNA-binding dye, such as propidium
iodide.26 27 28 These dyes stain the DNA in cells
with increased permeability of the nuclear envelope. Ultrastructural
techniques must then be applied to ensure the differentiation between
necrotic and apoptotic cells.
|
In Situ Hybridization
Two procedures have been developed that allow in situ detection of
apoptosis in formalin-fixed or paraffin-embedded tissue:
terminal deoxynucleotidyl transferase
(TdT)–mediated dUTP-biotin nick end labeling (TUNEL) and in situ end
labeling (ISEL). Both of these techniques rely on the occurrence of
internucleosomal DNA fragmentation by an endonuclease into
characteristic 180- to 200-bp segments.24
Staining with TUNEL is the classic in situ technique for detecting
apoptosis (see Figure 3). DNA
breaks are labeled within individual nuclei at the 3'-OH end with
biotinylated deoxyuridine. This signal is then amplified by
avidin-peroxidase.29 The ISEL technique utilizes
DNA polymerase to incorporate biotinylated nucleotides at
the DNA strand breaks.30 The benefits of these
techniques are the ability to evaluate a whole section of tissue. The
specificity of TUNEL staining has been questioned in recent
investigations, since necrotic cells have also been shown at times to
stain with this technique.31 Therefore, studies
using TUNEL staining as their only method of detecting
apoptosis should be considered
cautiously.32 An additional difficulty with using
TUNEL staining in atherosclerotic tissue has been labeling of matrix
vesicles by this technique.
|
Agarose Gel Electrophoresis (DNA Laddering)
The regular cleavage pattern of 180 to 200 bp of DNA created by
endonucleases as part of apoptosis creates the classic pattern
of DNA laddering when the DNA is evaluated by gel electrophoresis (see
Figure 4). This is quite different from
necrosis, wherein the DNA breakdown is random and leads to
irregular-length DNA fragments and an indistinct pattern on gel
electrophoresis.24 However, apoptosis may
occur even without the presence of a DNA ladder pattern on gel
electrophoresis in certain cell types.33 34
Nevertheless, apoptosis can be incited by adding endonuclease
into cells and inhibited by antibody directed toward endonuclease,
further supporting the role of this enzyme in
apoptosis.35 36 Thus, the finding of a
regular pattern of DNA fragmentation on gel electrophoresis is still
suggestive of apoptosis, but its absence does not exclude
apoptosis.
|
Flow Cytometry
This technique utilizes the flow cytometer to rapidly
analyze large numbers of single cells in suspension from either
homogeneous or heterogeneous cell
populations.37 With the use of
fluorescent dyes, flow cytometry can quantitatively measure the
amount of immunofluorescence of individual cells,
and the cells can then be classified based on the
immunofluorescent intensity. Although flow cytometry has been
used mainly to characterize peripheral blood cells, this
technique may also be used to characterize other cell
types.38 However, this technique is limited to
cells that can be placed into single-cell suspensions and may not be
used for tissues.39 An additional advantage of
this method is that in heterogeneous populations,
immunophenotyping can be added to characterize the cell types.
To evaluate apoptosis by flow cytometry, multiple known parameters of apoptosis have been employed. These include DNA degradation; reduction in cell volume; and structural changes such as increased plasma membrane permeability, altered intracellular ions, enhanced production of specific gene products associated with apoptosis, and altered plasma and mitochondrial membrane polarity.37 40 41
|
Biochemical and Genetic Controls of Apoptosis |
|---|
|
TopAbstractIntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
There are 4 stages of apoptosis: the initiation or stimulus for cell death, the active programmed cell death when the events become irreversible, phagocytosis of the dead cellular material, and inhibitory mechanisms of apoptosis. Some of the major stimuli and inhibitors of apoptosis are summarized in Table 2
and diagrammed in
Figure 5. Initiation of apoptosis
can result from multiple stimuli, including heat, toxins, free
radicals, growth factor withdrawal, cytokines such as
transforming growth factor-ß, loss of matrix attachment,
glucocorticoids, nitric oxide, and
radiation.19 42 These stimuli work in conjunction
with other intrinsic factors that determine the cell's potential to
undergo apoptosis. For example, smooth muscle cells from a
normal blood vessel undergo a high rate of apoptosis with the
withdrawal of growth factors such as insulin-like growth factor and
platelet-derived growth factor, whereas plaque-derived smooth
muscle cells proceed to apoptosis at a high rate even in the
presence of these important growth factors and at an even higher rate
without them.43 Cell type and basal conditions of
the cell, including cell cycle and differentiation, markedly influence
the likelihood of whether a cell will undergo apoptosis.
Moreover, many genes in the complex system of apoptosis
regulation also control the cell cycle and cell differentiation,
further demonstrating a complex interaction between these 2
processes.
|
|
(IFN),
interleukin-1 (IL-1), and Fas activation can all lead to activation of
either neutral or basic sphingomyelinases that cleave sphingolipids
into ceramide. Fas can be stimulated by nitric oxide, which in turn is
inhibited by angiotensin II. Ceramide activates
proteinases including the caspases (otherwise known as the ICE family
of proteases and other ICE-like proteases, such as CPP32) that mediate
intracellular protein degradation. Ceramide also actives endonucleases
that are responsible for DNA cleavage. Zinc (Zn) inhibits endonuclease,
and decreased intracellular pH activates it. Endonucleases are
also activated by caspases. Bcl-2 can inactivate
the caspases and therefore inhibit apoptosis. Bax forms a
heterodimer with bcl-2 and inactivates bcl-2 and is
therefore a permissive factor in apoptosis.Fas is a cell surface molecule that typically induces apoptosis.44 This mediator is important in controlling cell death in transformed cells, regulating normal immune responses, and ensuring self-recognition.45 46 In certain conditions, Fas activation also regulates T-cell activation and proliferation.47 Fas-induced apoptosis may be mediated through the sphingomyelin pathway, which leads to ceramide accumulation. Ceramide is an important mediator of apoptosis induced by both the sphingomyelin pathway and via activation of ceramide synthase.48 Another well-described regulator of apoptosis is c-myc, an example of how the regulation of cellular proliferation and apoptosis can be coupled. This proto-oncogene encodes for a DNA-binding protein that modulates transcription and can act as both a potent inducer of proliferation and a promoter of apoptosis.49 Evidence from increased levels of c-myc in many tumors emphasizes the importance of this gene in proliferation, but cytokines or oncogenes are required to block the apoptotic effects of c-myc.50 Thus, the regulation of cellular proliferation and apoptosis by c-myc is linked and modified through the cellular environment.
The interleukin-converting enzyme (ICE) family of proteases, more recently renamed the caspases, is a novel family of cytoplasmic cysteine proteases related to interleukin-1ß–converting enzyme (caspase-1).51 Caspases are believed to play a central role in the apoptosis cell signaling pathway.52 Inhibitors of caspases cause cells to be resistant to apoptosis when stimulated by multiple mechanisms.53 54 55 This finding supports the theory that multiple stimuli favoring apoptosis converge on 1 or a few central pathways from which the action of cell death proceeds. Although there is supporting evidence for the role of the caspases in apoptosis, it is yet unclear what the exact role this enzyme family has and how the different family members interact.
The bcl-2 protein, which is a membrane-associated protein of the mitochondria, nuclear envelope, and endoplasmic reticulum, is a potent inhibitor of apoptotic cell death.56 In gene transfer experiments, elevated levels of bcl-2 protein inhibited a number of apoptosis-promoting stimuli, including radiation, antineoplastic agents that cause nuclear damage, viral infection, growth factor withdrawal, and cytotoxic lymphokines.57 Excess bcl-2 expression in various cell types can lead to inhibition of apoptosis and is an important oncogenic factor in follicular lymphoma.58 59 Although this protein is important in the suppression of cell death, other members of the bcl family may activate cell death.60 61 This again emphasizes that apoptosis and cellular growth may be regulated in a coordinate fashion.
|
Apoptosis in Coronary Diseases |
|---|
|
TopAbstractIntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
Cell loss in atherosclerosis has been known since 1858, when Virchow described atherosclerosis as a process of replication of cells within the plaque followed by the death of these cells.62 More recently, with the further understanding of the mechanisms of apoptosis, there has been a resurgence in the interest in the mechanisms governing cell death associated with atherosclerosis.
Multiple studies in both animals and humans have found
apoptosis in atherosclerotic coronary, carotid, and
aortic arteries.14 15 63 The major studies are
summarized in Table 3. These studies have
shown that smooth muscle cells principally located in the intimal
fibrotic portion of the atherosclerotic plaque and macrophages
located in the intima, especially the lipid-laden core of the
atheroma, show increased evidence of apoptosis
compared with normal vessels.14 15
Apoptosis is also found in smooth muscle cells of the media
underlying atherosclerotic lesions and in conjunction with the vasa
vasorum and perivascular cells of the adventitia in human
atherosclerotic tissue.63 Furthermore, in
atherosclerotic tissue apoptosis is associated with the
formation of matrix vesicles rich in calcium and has led to the
proposal that apoptosis may be important in the
calcification of atherosclerotic tissue.68 It is
yet unclear whether apoptosis is a late finding as part of the
end stage of this disease or whether increased apoptosis is
associated with the early stages of atherogenesis. In
atherosclerosis, evidence supports the role of
apoptosis in vascular remodeling; apoptosis may be
beneficial by preventing excessive cellular proliferation.
|
Transplant coronary arteriopathy is a form of accelerated atherosclerosis. In transplant coronary arteriopathy nearly 100% of all endothelial cells and one third of T lymphocytes and macrophages express the Fas receptor. Whereas, there is virtually no expression of the Fas receptor in typical atherosclerotic coronary disease and in normal controls.16 Additionally, endothelial cells, T lymphocytes, and macrophages are positive for TUNEL staining, and nearly all TUNEL-positive cells are Fas-positive in the tissue from the transplant patients. Although Fas positivity in smooth muscle cells and immune cells is associated with induction of apoptosis, Fas may not trigger apoptosis in endothelial cells.66 Thus, the significance of Fas on endothelial cells in transplant arteriopathy is speculative. However, the observation that apoptosis as well as cell proliferation is prominent in transplant arteriopathy supports the hypothesis that apoptosis is involved in the early stages of this accelerated form of coronary artery disease.
Restenosis is also a process of excess cellular proliferation in atherosclerotic vessels. Restenotic lesions have a higher degree of medial smooth muscle cell apoptosis compared with native atherosclerotic lesions.69 Apoptosis in atherectomy specimens from restenotic tissue shows a different pattern compared with atherosclerotic tissue, with restenotic tissue displaying foci of increased apoptosis compared with a lower incidence of apoptosis in a more diffuse pattern in the atherosclerotic tissue. An important mitogen, basic fibroblast growth factor (FGF), is prominently expressed in restenosis as well as in intimal hyperplasia after endothelial denudation and in unstable coronary plaques. Inhibition of basic FGF induces apoptosis.67 Therefore, 1 mechanism by which restenosis occurs may be via FGF inhibition of apoptosis, thus favoring the balance toward cellular proliferation. Additionally, in animal studies, apoptosis is prominent in the vascular smooth muscle cells within 30 minutes after balloon injury.64 Furthermore, apoptosis remains increased in the neointima at least 1 month after injury.65 When stent implantation was compared with balloon injury, both medial smooth muscle cell proliferation and apoptosis were increased.70 Additionally, despite an equal rate of cellular proliferation in the neointima, stenting was associated with increased neointimal apoptosis, macrophage accumulation, and increased extracellular matrix secretion. Thus, regulation of the balance between cellular proliferation and apoptosis appears to be a major determinant of restenosis.
In human saphenous vein grafts stenosis is secondary to myointimal thickening and an associated luminal accumulation of foam cells with overlying thrombus.71 The foam cells prominently stain for markers of proliferation (Ki-67 and proliferating cell nuclear antigen), but in adjacent areas of the vessel there was progression to hypocellular regions of smooth muscle cells with increased apoptosis.71 The spatial association of foam cells with smooth muscle cell loss suggests that these foam cells may mediate smooth muscle cell apoptosis.71 Therefore, this study supports the hypothesis that the apoptotic process is intimately associated with the proliferative process.
Apoptosis is also associated with the
atherosclerosis risk factors of hypertension and
hypercholesterolemia. With the use of explant
techniques, cultured aortic vascular smooth muscle cells from
spontaneously hypertensive animals showed increased proliferation
characterized by increased growth rates with increased
[3H]leucine and
[14C]leucine incorporation even after multiple
passages.72 Additionally, cultured vascular
smooth muscle cells from the aortas of hypertensive rats had a greater
apoptotic response to apoptosis inducers such as
transforming growth factor-ß and tumor necrosis
factor-
.73 Thus, the enhanced cell
proliferation in hypertensive animals is paralleled by increased
susceptibility to apoptosis. Additionally, decreases in
intracellular pH are an important step in apoptosis, and
intracellular alkalinization is 1 mechanism to prevent
apoptosis. Thus, increased
Na+-H+ antiporter activity
in hypertension may lead to alterations in proliferation and
apoptosis regulation.74 Therefore,
hypertrophy of target organs and proliferation of the
vascular wall may be followed by atrophy induced by excessive
apoptosis of tissues in hypertensive
states.75 Treatment of this complex systemic
disease with agents like angiotensin-converting enzyme
inhibitors that interfere with the proliferative pathway
may help to restore the balance between proliferation and
apoptosis.76 Furthermore, different
antihypertensive agents have diverse effects on the rate of
apoptosis.77 Controlling abnormal
regulation of both proliferation and apoptosis may therefore be
an important treatment strategy.
In coronary atherosclerosis,
cholesterol may be important in the induction of
apoptosis. Although cholesterol itself has no
direct angiotoxicity, it forms cholesterol oxides that have
multiple toxic effects on the vasculature.78
Cholesterol oxides, including
7ß-hydroxycholesterol, 7-ketocholesterol,
19-hydroxycholesterol, cholesterol
5,-6-epoxide, and 25-hydroxycholesterol all promote
the loss of cell adhesion and increase the rate of apoptosis in
cultured endothelial cells.79
Cholesterol oxides promote disruption of actin
microfilaments, most notably with the disappearance of stress fibers
within the cell body.80 Additionally, oxidized
LDL increases apoptosis in vitro in a dose-dependent fashion
and is associated with increased caspase-3, 1 of the ICE-like proteases
also known as CPP32.81 Caspase-3 cleaves actin in
cell-free extracts, which may be 1 mechanism by which
cholesterol oxides can cause
apoptosis.82 However, the role of
apoptosis in hypercholesterolemia and
early atherosclerosis in vivo remains to be proven.
Vasoactive substances that are often altered in atherosclerosis are regulators of apoptosis. Nitric oxide, an important mediator of vasodilatation, platelet inhibition, and suppression of smooth muscle proliferation, upregulates Fas and induces apoptosis in vascular smooth muscle cells.18 19 83 Other vasodilators such as atrial natriuretic peptide and C-type natriuretic peptide also induce apoptosis in vascular smooth muscle cells.84 Additionally, angiotensin II, a mitogen and vasoconstricting peptide, antagonizes nitric oxide–induced apoptosis.19 Another important vasoconstricting peptide, endothelin-1, also counterbalances apoptotic promoters, and endothelin receptor antagonism is associated with increased apoptosis.20 22 It may be speculated that the critical balance between vasodilators that are growth inhibitors and vasoconstrictors that are growth promotors may involve the apoptotic process. Abnormalities in this balance associated with atherosclerosis may be 1 mechanism of atherosclerosis progression.
Thus, it has been demonstrated that apoptosis is present in atherosclerotic and postangioplasty lesions and confirmed by the additional findings of increases in other known markers of apoptosis. Apoptosis may be enhanced through multiple mechanisms including those associated with hypertension and hypercholesterolemia. The essential regulatory system of cell proliferation and apoptosis is fundamentally important to mediate responses to injury and the subsequent pathological processes in the blood vessels.
In summary, dysregulation of cell proliferation and apoptosis are clearly seen in multiple forms of vascular disease, including hypertension, transplant arteriopathy, and atherosclerosis. Apoptosis may play a significant role in the pathogenesis of coronary atherosclerosis and may be initiated by atherosclerotic risk factors. Previous studies support the hypothesis that a central balance between vasodilators with antimitogenic properties and vasoconstrictors with growth-promoting abilities is a major determinant of the response to injury and the effects of remodeling on the vessel wall. It may be speculated that one of the mechanisms by which this balance contributes to progression or repair in atherosclerosis is through regulation of cell apoptosis. A better understanding of the mediation of these events and a better knowledge of the role of proliferation and apoptosis in the pathophysiology of these disorders will further our understanding of cardiovascular disease and will help us to tailor therapeutic options to some of these important regulatory mechanisms.
|
Acknowledgments |
|---|
This work was supported by the Mayo Foundation, National Institutes of Health training grant HL07111-21D, the Bruce and Ruth Rappaport Program in Vascular Biology, and the Miami Heart Research Institute (to A.L.).
Received January 15, 1998; accepted June 11, 1998.
|
References |
|---|
|
TopAbstractIntroductionMethods to Detect ApoptosisBiochemical and Genetic Controls...Apoptosis in Coronary DiseasesReferences |
|---|
1. Kerr JFR, Wyllie AH, Currie AR. Apoptosis: a basic biologic phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer. 1972;26:239–257.[Medline] [Order article via Infotrieve]
2. Wyllie AH, Arends MJ, Morris RG, Walker SW, Evan G. The apoptosis endonuclease and its regulation. Semin Immunol. 1992;4:389–397.[Medline] [Order article via Infotrieve]
3. Rowan S, Fisher DE. Mechanisms of apoptotic cell death. Leukemia. 1997;11:457–465.[Medline] [Order article via Infotrieve]
4.
Sachs L. The control of hematopoiesis and leukemia:
from basic biology to the clinic. Proc Natl Acad Sci
U S A. 1996;93:4742–4749.
5. Risau W, Flamme I. Vasculogenesis. Annu Rev Cell Dev Biol.. 1995;11:73–91.[Medline] [Order article via Infotrieve]
6. Haanen C, Vermes I. Apoptosis: programmed cell death in fetal development. Eur J Obstet Gynecol Reprod Biol. 1996;64:129–133.[Medline] [Order article via Infotrieve]
7. Ellis PA, Smith IE, Dowsett M. Apoptosis: its role in tumour growth and therapy. Cytopathology. 1996;7:201–203.[Medline] [Order article via Infotrieve]
8. Ameisen JC. Programmed cell death (apoptosis) and cell survival regulation: relevance to AIDS and cancer. AIDS. 1994;8:1197–1213.[Medline] [Order article via Infotrieve]
9. Yao M, Keogh A, Spratt P, dos Remedios CG, Kiessling PC. Elevated DNase I levels in human idiopathic dilated cardiomyopathy: an indicator of apoptosis? J Mol Cell Cardiol. 1996;28:95–101.[Medline] [Order article via Infotrieve]
10. Cheng W, Kajstura J, Nitahara JA, Li B, Reiss K, Liu Y, Clark WA, Krajewski S, Reed JC, Olivetti G, Anversa P. Programmed myocyte cell death affects the viable myocardium after infarction in rats. Exp Cell Res. 1996;226:316–327.[Medline] [Order article via Infotrieve]
11.
Mallat Z, Tedgui A, Fontaliran F, Frank R, Duigon M,
Fontaine G. Evidence of apoptosis in arrhythmogenic right
ventricular dysplasia. N Engl J Med. 1996;335:1190–1196.
12. James TN. Long reflections on the QT interval: the sixth annual Gordon K. Moe Lecture. J Cardiovasc Electrophysiol. 1996;7:738–759.[Medline] [Order article via Infotrieve]
13.
James TN, St Martin E, Willis PW 3rd, Lohr TO.
Apoptosis as a possible cause of gradual development of
complete heart block and fatal arrhythmias associated with
absence of the AV node, sinus node, and internodal pathways.
Circulation. 1996;93:1424–1438.
14. Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma: colocalization with interleukin-1ß-converting enzyme. Am J Pathol. 1995;147:251–266.[Abstract]
15. Bochaton-Piallat ML, Gabbiani F, Redard M, Desmouliere A, Gabbiani G. Apoptosis participates in cellular regulation during rat aortic intimal thickening. Am J Pathol. 1995;146:1059–1064.[Abstract]
16. Dong C, Wilson JE, Winters GL, McManus BM. Human transplant coronary artery disease: pathologic evidence for Fas mediated apoptotic cytotoxicity in allograft arteriopathy. Lab Invest. 1996;74:921–931.[Medline] [Order article via Infotrieve]
17.
Mallat Z, Ohan J, Leseche G, Tedgui A. Colocalization
of CPP-32 with apoptotic cells in human atherosclerotic
plaques. Circulation. 1997;96:424–428.
18.
Fukuo K, Hata S, Suhara T, Nakahashi T, Shinto Y,
Tsujimoto Y, Morimoto S, Ogihara T. Nitric oxide induces upregulation
of Fas and apoptosis in vascular smooth muscle.
Hypertension. 1996;27:823–826.
19.
Pollman MJ, Yamada T, Horiuchi M, Gibbons GH.
Vasoactive substances regulate vascular smooth muscle cell
apoptosis. Circ Res. 1996;79:748–756.
20.
Shichiri M, Kato H, Marumo F, Hirata Y. Endothelin-1 as
an autocrine/paracrine apoptosis survival factor for
endothelial cells. Hypertension. 1997;30:1198–1203.
21.
Dimmeler S, Rippmann V, Weiland U, Haendeler J, Zeiher
AM. Angiotensin II induces apoptosis of human
endothelial cells: protective effect of nitric oxide.
Circ Res. 1997;81:970–976.
22. Sharifi AM, Schriffrin EL. Apoptosis in aorta of deoxycorticosterone acetate-salt hypertensive rats: effects of endothelin receptor antagonism. J Hypertens. 1997;15(pt 1):1441–1448.
23. Kerr JFR. A histochemical study of hypertrophy and ischaemic injury of rat liver with special references to changes in lysosomes. J Pathol Bacteriol. 1965;90:419–435.[Medline] [Order article via Infotrieve]
24. Majno G, Joris I. Apoptosis, oncosis, and necrosis. an overview of cell death. Am J Pathol. 1995;146:3–15.[Abstract]
25. Kerr JFR, Gobé GC, Winterford CM, Harmon BV. Anatomic methods in cell death. Methods Cell Biol. 1995;46:1–27.[Medline] [Order article via Infotrieve]
26. Crompton T, Peitsch MC, MacDonald HR, Tschopp J. Propidium iodide staining correlates with the extent of DNA degradation in isolated nuclei. Biochem Biophys Res Commun. 1992;183:532–537.[Medline] [Order article via Infotrieve]
27. Tounekti O, Belehradek J Jr, Mir LM. Relationship between DNA fragmentation, chromatin condensation, and changes in flow cytometry profiles detected during apoptosis. Exp Cell Res. 1995;217:506–516.[Medline] [Order article via Infotrieve]
28. Kimura K, Sasano H, Shimosegawa T, Kato K, Noguchi T, Mochizuki S, Sawai T, Koizumi M, Totyota T, Nagura H. Ultrastructural and confocal laser scanning microscopic examination of TUNEL-positive cells. J Pathol. 1997;181:235–242.[Medline] [Order article via Infotrieve]
29.
Gavrieli Y, Sherman Y, Ben-Sasson SA. Identification of
programmed cell death in-situ via specific labeling of nuclear DNA
fragmentation. J Cell Biol. 1992;119:493–501.
30. Kockx MM, De Meyer GRY, Muhring J, Bult H, Bultinck J, Herman AG. Distribution of cell replication and apoptosis in atherosclerotic plaque of cholesterol-fed rabbits. Atherosclerosis. 1996;120:115–124.[Medline] [Order article via Infotrieve]
31. Grasl-Kraupp B, Ruttkay-Nedecky B, Koudelka H, Bukowska K, Bursch W, Schulte-Hermann R. In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note. Hepatology. 1995;21:1465–1468.[Medline] [Order article via Infotrieve]
32. Charriaut-Marlangue C, Ben-Ari Y. A cautionary note on the use of the TUNEL stain to determine apoptosis. Neuroreport. 1995;7:61–64.[Medline] [Order article via Infotrieve]
33. Marini M, Musiani D, Sestili P, Cantoni O. Apoptosis of human lymphocytes in the absence or presence of internucleosomal DNA cleavage. Biochem Biophys Res Commun. 1996;229:910–915.[Medline] [Order article via Infotrieve]
34. Cohen GM, Sun XM, Snowden RT, Dinsdale D, Skilleter DN. Key morphological features of apoptosis may occur in the absence of internucleosomal DNA fragmentation. Biochem J. 1992;286(pt 2):331–334.
35. Samaha H, Berstein C, Payne C, Asher E. Evaluation of cell death in EBV-transformed lymphocytes using agarose gel electrophoresis: light microscopy and electron microscopy, I: induction of classic apoptosis by the bile salt, sodium deoxycholate. Leuk Lymphoma. 1995;19:95–105.[Medline] [Order article via Infotrieve]
36. Peitsch MC, Polzar B, Stephan H, Crompton T, MacDonald HR, Mannerherz HG, Tschopp J. Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death). EMBO J. 1993;12:371–377.[Medline] [Order article via Infotrieve]
37. Franker PJ, King LE, Lill-Elghanian D, Telford WG. Quantification of apoptotic events in pure and heterogeneous populations of cells using the flow cytometer. Methods Cell Biol. 1995;46:57–76.[Medline] [Order article via Infotrieve]
38. Carbonari M, Cibati M, Fiorilli M. Measurement of apoptotic cells in peripheral blood. Cytometry. 1995;22:161–167.[Medline] [Order article via Infotrieve]
39. Mesner PW Jr, Kaufmann SH. Methods utilized in the study of apoptosis. Adv Pharmacol. 1997;41:57–87.
40. Telford WG, King LE, Franker PJ. Evaluation of glucocorticoid-induced DNA fragmentation in thymocytes by flow cytometry. Cell Prolif. 1991;24:447–459.[Medline] [Order article via Infotrieve]
41. Sherwood SW, Schimke RT. Cell cycle analysis of apoptosis using flow cytometry. Methods Cell Biol. 1995;46:77–97.[Medline] [Order article via Infotrieve]
42.
Thompson CB. Apoptosis in the pathogenesis and
treatment of disease. Science. 1995;267:1456–1462.
43. Bennett MR, Evan GI, Schwartz SM. Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest. 1995;95:2266–2274.
44.
Nagata S, Golstein P. The Fas death factor.
Science. 1995;267:1449–1456.
45. Wantanabe-Fukunaga R, Brannan CI, Copland NG, Jenkins NA, Nagata S. Lymphoproliferative disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–317.[Medline] [Order article via Infotrieve]
46. Takahashi T, Tanaka M, Brannan CI, Jenkins NA, Copeland NG, Suda T, Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994;76:969–976.[Medline] [Order article via Infotrieve]
47.
Alderson MR, Armitage RJ, Marakovsky E, Tough TW, Roux
E, Schooley K, Ramsdell F, Lynch DH. Fas transduces activation signals
in normal human T lymphocytes. J Exp Med. 1993;178:2231–2235.
48. Bose R, Verheij M, Haimovitz-Friedman A, Scotto K, Fuks Z, Kolesnick R. Ceramide synthase mediates daunorubacin-induced apoptosis: a new mechanism for generating death signals. Cell. 1995;82:405–414.[Medline] [Order article via Infotrieve]
49. Evan G, Wyllie A, Gilbert C, Littlewood T, Land H, Brooks M, Walters C, Penn L, Hancock D. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992;63:119–125.
50. Desbarats L, Schneider A, Muller D, Burgin A, Eilers M. Myc: a single gene controls both proliferation and apoptosis in mammalian cells links external signals to cell cycle machinery. Experientia. 1996;52:1123–1129.[Medline] [Order article via Infotrieve]
51. Miura M, Zhu H, Rotello R, Hartwig EA, Yuan J. Induction of apoptosis in fibroblasts by IL-1 ß-converting enzyme, a mammalian homologue of the C. elegans cell death gene ced-3. Cell. 1993;75:653–660.[Medline] [Order article via Infotrieve]
52. Zhu H, Fearnhead HO, Cohen GM. An ICE-like protease is a common mediator of apoptosis induced by diverse stimuli in human monocytic THP 1 cells. FEBS Lett. 1995;374:303–308.[Medline] [Order article via Infotrieve]
53.
Boudreau N, Sympson CJ, Werb Z, Bissell MJ. Suppression
of ICE and apoptosis in mammary epithelial cells by
extracellular matrix. Science. 1995;267:891–893.
54.
Tewardi M, Dixit VM. Fas- and tumor necrosis
factor-induced apoptosis is inhibited by poxvirus crmA gene
product. J Biol Chem. 1995;270:3255–3260.
55.
Miuri M, Friedlander RM, Yuan J. Tumor necrosis
factor-induced apoptosis is mediated by a CrmA-sensitive cell
death pathway. Proc Natl Acad Sci U S A. 1995;92:8318–8322.
56. Jacobson MD, Burne JF, King MP, Miyashita T, Reed JC, Raff MC. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993;361:365–369.[Medline] [Order article via Infotrieve]
57.
Reed JC. Bcl-2 and the regulation of programmed cell
death. J Cell Biol. 1994;124:1–6.
58. Hockenbery DM. The bcl-2 gene and apoptosis. Semin Immunol. 1992;4:413–420.[Medline] [Order article via Infotrieve]
59. Reed JC, Cuddy M, Slabiak T, Croce CM, Nowell PC. Oncogenic potential of bcl-2 demonstrated by gene transfer. Nature. 1988;336:259–261.[Medline] [Order article via Infotrieve]
60. Takayama S, Cazals-Hatem DL, Kitada S, Tanaka S, Miyashi T, Hovey LR, Huen D, Rickinson A, Veerapandian P, Krajewski S, Saito K, Reed JC. Evolutionary conservation of function among mammalian, avian, and viral homologues of the bcl-2 oncoprotein: structure-function implications. DNA Cell Biol. 1994;13:679–692.[Medline] [Order article via Infotrieve]
61. Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB. BCL-x, a bcl-2 related gene that functions as a dominant receptor of apoptotic cell death. Cell. 1993;74:597–608.[Medline] [Order article via Infotrieve]
62. Schwartz SM, Bennett MR. Death by another name. Am J Pathol. 1995;147:229–234.[Medline] [Order article via Infotrieve]
63. Bjorkerud S, Bjorkerud B. Apoptosis is abundant in human atherosclerotic lesions, especially in inflammatory cells (macrophages and T cells), and may contribute to the accumulation of gruel and plaque instability. Am J Pathol. 1996;149:367–380.[Abstract]
64.
Perlman H, Maillard L, Krasinski K, Walsh K. Evidence
for the rapid onset of apoptosis in medial smooth muscle cells
after balloon injury. Circulation. 1997;95:981–987.
65. Han DKM, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherogenesis and in a rat model vascular injury model. Am J Pathol. 1995;147:267–277.[Abstract]
66. Richardson BC, Lalwani ND, Johnson KJ, Marks RM. Fas ligation triggers apoptosis in macrophages but not endothelial cells. Eur J Immunol. 1994;24:2640–2645.[Medline] [Order article via Infotrieve]
67.
Fox JC, Shanley JR. Antisense inhibition of basic
fibroblast growth factor induces apoptosis in vascular smooth
muscle cells. J Biol Chem. 1996;271:12578–12584.
68. Kockx MM, Muhring J, Bortier H, De Meyer GRY, Jacob W. Biotin- or digoxigenin-conjugated nucleosides bind to matrix vesicles in atherosclerotic plaques. Am J Pathol. 1996;148:1771–1777.[Abstract]
69.
Isner JM, Kearney M, Bortman S, Passeri J.
Apoptosis in human atherosclerosis and
restenosis. Circulation. 1995;91:2703–2711.
70.
Kollum M, Kaiser S, Kinscherf R, Metz J, Kubler W,
Hehrlein C. Apoptosis after stent implantation compared with
balloon angioplasty in rabbits: role of macrophages.
Arterioscler Thromb Vasc Biol. 1997;17:2383–2388.
71.
Kockx MM, De Meyer GRY, Bortier H, de Meyere N, Muhring
J, Bakker A, Jacob W, Van Vaeck L, Herman A. Luminal foam cell
accumulation is associated with smooth muscle cell death in the intimal
thickening of human saphenous vein grafts. Circulation. 1996;94:1255–1262.
72. Yamori Y, Igawa T, Kanbe T, Kihara M, Naara M, Naara Y, Horie R. Mechanisms of structural vascular changes in genetic hypertension: analyses on culture vascular smooth muscle cells from spontaneously hypertensive rats. Clin Sci. 1981;61:121S–123S.
73.
Hamet P, Richard L, Dam TV, Teiger E, Orlov SN, Gaboury
L, Gossard F, Tremblay J. Apoptosis in target organs of
hypertension. Hypertension. 1995;26:642–648.
74.
Caceres-Cortes J, Rajotte D, Dumouchel J, Haddad P,
Hoang T. Product of the steel locus suppress apoptosis in
hematopoietic cells: comparison with pathways activated by
granulocyte macrophage colony-stimulating factor. J
Biol Chem. 1994;269:12084–12091.
75. Hamet P. Proliferation and apoptosis of the vascular smooth muscle in hypertension. Curr Opin Nephrol Hypertens. 1995;4:1–7.[Medline] [Order article via Infotrieve]
76.
Jackson CL, Schwartz SM. Pharmacology of smooth muscle
cell replication. Hypertension. 1992;20:713–736.
77. deBlois D, Tea BS, Than VD, Tremblay J, Hamet P. Smooth muscle cell apoptosis during vascular regression in spontaneously hypertensive rats. Hypertension. 1997;29(pt 2):340–349.
78.
Imai H, Werthessen NT, Subramayam V, Lequesne PW,
Soloway AH, Kanisawa M. Angiotoxicity of oxygenates sterols
and possible precursors. Science. 1980;207:651–653.
79. Lizard G, Deckert V, Dubrez L, Moisant M, Gambert P, Lagrost L. Induction of apoptosis in endothelial cells treated with cholesterol oxides. Am J Pathol. 1996;148:1625–1638.[Abstract]
80. Palladini G, Finardi G, Bellomo G. Disruption of actin microfilament organization by cholesterol oxides in 73/73 endothelial cells. Exp Cell Res. 1996;223:72–82.[Medline] [Order article via Infotrieve]
81.
Dimmeler S, Haendeler J, Galle J, Zeiher AM. Oxidized
low-density lipoprotein induces apoptosis of human
endothelial cells by activation of CPP32-like protease.
Circulation. 1997;95:1760–1763.
82.
Song Q, Wei T, Lees-Miller S, Alnemri E, Watters D,
Lavin MF. Resistance of actin to cleavage during apoptosis.
Proc Natl Acad Sci U S A. 1997;94:157–162.
83. Nishio E, Fukuahima K, Shiozaki M, Watanabe Y. Nitric oxide donor SNAP induces apoptosis in smooth muscle cells through cGMP-independent mechanism. Biochem Biophys Res Commun. 1996;221:163–168.[Medline] [Order article via Infotrieve]
84. Trindade P, Hutchinson HG, Pollman MJ, Gibbons GH, Pratt RE. Atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP) induce apoptosis in vascular smooth muscle cells (VSMC). Circulation. 1995;92(suppl I):I-696. Abstract.
This article has been cited by other articles:
 |
|
 |
|
  G. J Allan, J. Beattie, and D. J Flint Epithelial injury induces an innate repair mechanism linked to cellular senescence and fibrosis involving IGF-binding protein-5 J. Endocrinol., November 1, 2008; 199(2): 155 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Sedding, M. Homann, U. Seay, H. Tillmanns, K. T. Preissner, and R. C. Braun-Dullaeus Calpain counteracts mechanosensitive apoptosis of vascular smooth muscle cells in vitro and in vivo FASEB J, February 1, 2008; 22(2): 579 - 589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Maiellaro and W. R. Taylor The role of the adventitia in vascular inflammation Cardiovasc Res, September 1, 2007; 75(4): 640 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Eiselein, D. W. Wilson, M. W. Lame, and J. C. Rutledge Lipolysis products from triglyceride-rich lipoproteins increase endothelial permeability, perturb zonula occludens-1 and F-actin, and induce apoptosis Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2745 - H2753. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C.H. Kwan, F. Kronenberg, S. Beddhu, and A. K. Cheung Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1246 - 1261. [Full Text] [PDF]
|
|
|
|
 |
|
 A K Mitra and D K Agrawal In stent restenosis: bane of the stent era. J. Clin. Pathol., March 1, 2006; 59(3): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Jagadeesha, T. E. Lindley, J. DeLeon, R. V. Sharma, F. Miller, and R. C. Bhalla Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1047 - H1053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Fries, P. Mahboubi, N. R. Mahapatra, S. K. Mahata, N. J. Schork, G. W. Schmid-Schoenbein, and D. T. O'Connor Neuroendocrine Transcriptome in Genetic Hypertension: Multiple Changes in Diverse Adrenal Physiological Systems Hypertension, June 1, 2004; 43(6): 1301 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Beohar, J. D. Flaherty, C. J. Davidson, R. C. Maynard, J. D. Robbins, A. P. Shah, J. W. Choi, L. A. MacDonald, J. P. Jorgensen, J. V. Pinto, et al. Antirestenotic Effects of a Locally Delivered Caspase Inhibitor in a Balloon Injury Model Circulation, January 6, 2004; 109(1): 108 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.O Bonetti, L.O Lerman, C Napoli, and A Lerman Statin effects beyond lipid lowering--are they clinically relevant? Eur. Heart J., February 1, 2003; 24(3): 225 - 248. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Herrmann, W. D. Edwards, D. R. Holmes Jr, K. L. Shogren, L. O. Lerman, A. Ciechanover, and A. Lerman Increased ubiquitin immunoreactivity in unstable atherosclerotic plaques associated with acute coronary syndromes J. Am. Coll. Cardiol., December 4, 2002; 40(11): 1919 - 1927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Shuhaiber, A. N. Evans, M. G. Massad, and A. S. Geha Mechanisms and future directions for prevention of vein graft failure in coronary bypass surgery Eur. J. Cardiothorac. Surg., September 1, 2002; 22(3): 387 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sotoudeh, Y.-S. Li, N. Yajima, C.-C. Chang, T.-C. Tsou, Y. Wang, S. Usami, A. Ratcliffe, S. Chien, and J. Y.-J. Shyy Induction of apoptosis in vascular smooth muscle cells by mechanical stretch Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1709 - H1716. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Granville, B. A. Cassidy, D. O. Ruehlmann, J. C. Choy, C. Brenner, G. Kroemer, C. van Breemen, P. Margaron, D. W. Hunt, and B. M. McManus Mitochondrial Release of Apoptosis-Inducing Factor and Cytochrome c During Smooth Muscle Cell Apoptosis Am. J. Pathol., July 1, 2001; 159(1): 305 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. H. Kown, A. Yamaguchi, C. L. Jahncke, D. Miniati, S. Murata, J. Grunenfelder, M. L. Koransky, J. B. Rothbard, and R. C. Robbins L-arginine polymers inhibit the development of vein graft neointimal hyperplasia J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 971 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-S. Lee and L.-Y. Chau Fas/Fas ligand-mediated death pathway is involved in oxLDL-induced apoptosis in vascular smooth muscle cells Am J Physiol Cell Physiol, March 1, 2001; 280(3): C709 - C718. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Golledge, R. M. Greenhalgh, and A. H. Davies The Symptomatic Carotid Plaque Stroke, March 1, 2000; 31(3): 774 - 781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. MAYR, C. LI, Y. ZOU, U. HUEMER, Y. HU, and Q. XU Biomechanical stress-induced apoptosis in vein grafts involves p38 mitogen-activated protein kinases FASEB J, February 1, 2000; 14(2): 261 - 270. [Abstract] [Full Text]
|
|
|
|
|
|
M. M Kockx and A. G Herman Apoptosis in atherosclerosis: beneficial or detrimental? Cardiovasc Res, February 1, 2000; 45(3): 736 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hishikawa, B. S. Oemar, F. C. Tanner, T. Nakaki, T. Fujii, and T. F. Luscher Overexpression of Connective Tissue Growth Factor Gene Induces Apoptosis in Human Aortic Smooth Muscle Cells Circulation, November 16, 1999; 100(20): 2108 - 2112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-K. Chang, C. Bergmark, A. Laurila, S. Horkko, K.-H. Han, P. Friedman, E. A. Dennis, and J. L. Witztum Monoclonal antibodies against oxidized low-density lipoprotein bind to apoptotic cells and inhibit their phagocytosis by elicited macrophages: Evidence that oxidation-specific epitopes mediate macrophage recognition PNAS, May 25, 1999; 96(11): 6353 - 6358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Buus, F. Pourageaud, G. E. Fazzi, G. Janssen, M. J. Mulvany, and J. G.R. De Mey Smooth Muscle Cell Changes During Flow-Related Remodeling of Rat Mesenteric Resistance Arteries Circ. Res., July 20, 2001; 89(2): 180 - 186. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||