Atherosclerosis is a multifactorial disease that involves several genes and proteins. The purpose of this article is to focus on the arterial wall and to review lipoprotein receptors, growth factors, cytokines, chemokines, matrix metalloproteinases, adhesion molecules, and apoptosis genes and their involvement in atherogenesis.

Keywords:
Lipoprotein receptors, Adhesion molecules, Growth factors, Inflammation, Matrix metalloproteinases, Apoptosis, Atherosclerosis
1.
Ross R: The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 1993;362:801–809.
2.
Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M: Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature 1990;343:531–535.
3.
Rohrer L, Freeman M, Kodama T, Penman M, Krieger M: Coiled-coil fibrous domains mediate ligand binding by macrophage scavenger receptor type II. Nature 1990;343:570–572.
4.
Gough PJ, Greaves DR, Gordon S: A naturally occurring isoform of the human macrophage scavenger receptor (SR-A) gene generated by alternative splicing blocks modified LDL uptake. J Lipid Res 1998;39:531–543.
5.
Ylä-Herttuala S, Rosenfeld ME, Parthasarathy S, et al: Gene expression in macrophage-rich human atherosclerotic lesions: 15-Lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts. J Clin Invest 1991;87:1146–1152.
6.
Greaves DR, Gough PJ, Gordon S: Recent progress in defining the role of scavenger receptors in lipid transport, atherosclerosis and host defence. Curr Opin Lipidol 1998;9:425–432.
7.
Hiltunen TP, Luoma JS, Nikkari T, Ylä-Herttuala S: Expression of LDL receptor, VLDL receptor, LDL receptor-related protein, and scavenger receptor in rabbit atherosclerotic lesions: Marked induction of scavenger receptor and VLDL receptor expression during lesion development. Circulation 1998;97:1079–1086.
8.
Naito M, Suzuki H, Mori T, Matsumoto A, Kodama T, Takahashi K: Coexpression of type I and type II human macrophage scavenger receptors in macrophages of various organs and foam cells in atherosclerotic lesions. Am J Pathol 1992;141:591–599.
9.
Suzuki H, Kurihara Y, Takeya M, et al: A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection. Nature 1997;386:292–296.
10.
Vlassara H, Brownlee M, Cerami A: High-affinity-receptor-mediated uptake and degradation of glucose-modified proteins: A potential mechanism for the removal of senescent macromolecules. Proc Natl Acad Sci USA 1985;82:5588–5592.
11.
Takata K, Horiuchi S, Araki N, Shiga M, Saitoh M, Morino Y: Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins. J Biol Chem 1988;263:14819–14825.
12.
el Khoury J, Thomas CA, Loike JD, Hickman SE, Cao L, Silverstein SC: Macrophages adhere to glucose-modified basement membrane collagen IV via their scavenger receptors. J Biol Chem 1994;269:10197–10200.
13.
Fraser I, Hughes D, Gordon S: Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor. Nature 1993;364:343–346.
14.
Platt N, da Silva RP, Gordon S: Class A scavenger receptors and the phagocytosis of apoptotic cells. Immunol Lett 1999;65:15–19.
15.
Terpstra V, Kondratenko N, Steinberg D: Macrophages lacking scavenger receptor A show a decrease in binding and uptake of acetylated low-density lipoprotein and of apoptotic thymocytes, but not of oxidatively damaged red blood cells. Proc Natl Acad Sci USA 1997;94:8127–8131.
16.
Yokota T, Ehlin-Henriksson B, Hansson GK: Scavenger receptors mediate adhesion of activated B lymphocytes. Exp Cell Res 1998;239:16–22.
17.
Dunne DW, Resnick D, Greenberg J, Krieger M, Joiner KA: The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid. Proc Natl Acad Sci USA 1994;91:1863–1867.
18.
Hampton RY, Golenbock DT, Penman M, Krieger M, Raetz CR: Recognition and plasma clearance of endotoxin by scavenger receptors. Nature 1991;352:342–344.
19.
Haworth R, Platt N, Keshav S, et al: The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med 1997;186:1431–1439.
20.
Lougheed M, Lum CM, Ling W, Suzuki H, Kodama T, Steinbrecher U: High affinity saturable uptake of oxidized low density lipoprotein by macrophages from mice lacking the scavenger receptor class A type I/II. J Biol Chem 1997;272:12938–12944.
21.
Ling W, Lougheed M, Suzuki H, Buchan A, Kodama T, Steinbrecher UP: Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A type I/II gene. J Clin Invest 1997;100:244–252.
22.
Sakaguchi H, Takeya M, Suzuki H, et al: Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice. Lab Invest 1998;78:423–434.
23.
de Winther MP, Gijbels MJ, van Dijk KW, et al: Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3 Leiden transgenic mice. Atherosclerosis 1999;144:315–321.
24.
van Eck M, de Winther MP, Herijgers N, et al: Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on cholesterol levels and atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 2000;20:2600–2606.
25.
Wolle S, Via DP, Chan L, Cornicelli JA, Bisgaier CL: Hepatic overexpression of bovine scavenger receptor type I in transgenic mice prevents diet-induced hyperbetalipoproteinemia. J Clin Invest 1995;96:260–272.
26.
Silverstein RL, Febbraio M: CD36 and atherosclerosis. Curr Opin Lipidol 2000;11:483–491.
27.
Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA: CD36 is a receptor for oxidized low density lipoprotein. J Biol Chem 1993;268:11811–11816.
28.
Huh HY, Lo SK, Yesner LM, Silverstein RL: CD36 induction on human monocytes upon adhesion to tumor necrosis factor-activated endothelial cells. J Biol Chem 1995;270:6267–6271.
29.
Huh HY, Pearce SF, Yesner LM, Schindler JL, Silverstein RL: Regulated expression of CD36 during monocyte-to-macrophage differentiation: Potential role of CD36 in foam cell formation. Blood 1996;87:2020–2028.
30.
Yesner LM, Huh HY, Pearce SF, Silverstein RL: Regulation of monocyte CD36 and thrombospondin-1 expression by soluble mediators. Arterioscler Thromb Vasc Biol 1996;16:1019–1025.
31.
Dawson DW, Pearce SF, Zhong R, Silverstein RL, Frazier WA, Bouck NP: CD36 mediates the in vitro inhibitory effects of thrombospondin-1 on endothelial cells. J Cell Biol 1997;138:707–717.
32.
Jimenez B, Volpert OV, Crawford SE, Febbraio M, Silverstein RL, Bouck N: Signals leading to apoptosis-dependent inhibition of neovascularization by thrombospondin-1. Nat Med 2000;6:41–48.
33.
Moulton KS, Heller E, Konerding MA, Flynn E, Palinski W, Folkman J: Angiogenesis inhibitors endostatin or TNP-470 reduce intimal neovascularization and plaque growth in apolipoprotein E-deficient mice. Circulation 1999;99:1726–1732.
34.
Ren Y, Silverstein RL, Allen J, Savill J: CD36 gene transfer confers capacity for phagocytosis of cells undergoing apoptosis. J Exp Med 1995;181:1857–1862.
35.
Maxeiner H, Husemann J, Thomas CA, Loike JD, el Khoury J, Silverstein SC: Complementary roles for scavenger receptor A and CD36 of human monocyte-derived macrophages in adhesion to surfaces coated with oxidized low-density lipoproteins and in secretion of H2O2. J Exp Med 1998;188:2257–2265.
36.
Febbraio M, Podrez EA, Smith JD, et al: Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. J Clin Invest 2000;105:1049–1056.
37.
Nakata A, Nakagawa Y, Nishida M, et al: CD36, a novel receptor for oxidized low-density lipoproteins, is highly expressed on lipid-laden macrophages in human atherosclerotic aorta. Arterioscler Thromb Vasc Biol 1999;19:1333–1339.
38.
Yamamoto N, Ikeda H, Tandon NN, et al: A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Naka-platelets lack detectable GPIV (CD36). Blood 1990;76:1698–1703.
39.
Curtis BR, Aster RH: Incidence of the Nak(a)-negative platelet phenotype in African Americans is similar to that of Asians. Transfusion 1996;36:331–334.
40.
Podrez EA, Febbraio M, Sheibani N, et al: Macrophage scavenger receptor CD36 is the major receptor for LDL modified by monocyte-generated reactive nitrogen species. J Clin Invest 2000;105:1095–1108.
41.
Tanaka T, Sohmiya K, Kawamura K: Is CD36 deficiency an etiology of hereditary hypertrophic cardiomyopathy? J Mol Cell Cardiol 1997;29:121–127.
42.
Acton S, Rigotti A, Landschulz KT, Xu S, Hobbs HH, Krieger M: Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science 1996;271:518–520.
43.
Rigotti A, Acton SL, Krieger M: The class B scavenger receptors SR-BI and CD36 are receptors for anionic phospholipids. J Biol Chem 1995;270:16221–16224.
44.
Bensadoun A, Berryman DE: Genetics and molecular biology of hepatic lipase. Curr Opin Lipidol 1996;7:77–81.
45.
Bamberger M, Glick JM, Rothblat GH: Hepatic lipase stimulates the uptake of high density lipoprotein cholesterol by hepatoma cells. J Lipid Res 1983;24:869–876.
46.
Kadowaki H, Patton GM, Robins SJ: Metabolism of high density lipoprotein lipids by the rat liver: Evidence for participation of hepatic lipase in the uptake of cholesteryl ester. J Lipid Res 1992;33:1689–1698.
47.
Wang N, Weng W, Breslow JL, Tall AR: Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores: In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control. J Biol Chem 1996;271:21001–21004.
48.
Kozarsky KF, Donahee MH, Rigotti A, Iqbal SN, Edelman ER, Krieger M: Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Nature 1997;387:414–417.
49.
Ueda Y, Royer L, Gong E, et al: Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice. J Biol Chem 1999;274:7165–7171.
50.
Arai T, Wang N, Bezouevski M, Welch C, Tall AR: Decreased atherosclerosis in heterozygous low density lipoprotein receptor-deficient mice expressing the scavenger receptor BI transgene. J Biol Chem 1999;274:2366–2371.
51.
Ueda Y, Gong E, Royer L, Cooper PN, Francone OL, Rubin EM: Relationship between expression levels and atherogenesis in scavenger receptor class B, type I transgenics. J Biol Chem 2000;275:20368–20373.
52.
Kozarsky KF, Donahee MH, Glick JM, Krieger M, Rader DJ: Gene transfer and hepatic overexpression of the HDL receptor SR-BI reduces atherosclerosis in the cholesterol-fed LDL receptor-deficient mouse. Arterioscler Thromb Vasc Biol 2000;20:721–727.
53.
Rigotti A, Trigatti BL, Penman M, Rayburn H, Herz J, Krieger M: A targeted mutation in the murine gene encoding the high density lipoprotein (HDL) receptor scavenger receptor class B type I reveals its key role in HDL metabolism. Proc Natl Acad Sci USA 1997;94:12610–12615.
54.
Krieger M: Charting the fate of the ‘good cholesterol’: Identification and characterization of the high-density lipoprotein receptor SR-BI. Annu Rev Biochem 1999;68:523–558.
55.
Sawamura T, Kume N, Aoyama T, et al: An endothelial receptor for oxidized low-density lipoprotein. Nature 1997;386:73–77.
56.
Kume N, Kita T: Roles of lectin-like oxidized LDL receptor-1 and its soluble forms in atherogenesis. Curr Opin Lipidol 2001;12:419–423.
57.
Li DY, Zhang YC, Philips MI, Sawamura T, Mehta JL: Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation. Circ Res 1999;84:1043–1049.
58.
Kume N, Murase T, Moriwaki H, et al: Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 1998;83:322–327.
59.
Murase T, Kume N, Korenaga R, et al: Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells. Circ Res 1998;83:328–333.
60.
Aoyama T, Fujiwara H, Masaki T, Sawamura T: Induction of lectin-like oxidized LDL receptor by oxidized LDL and lysophosphatidylcholine in cultured endothelial cells. J Mol Cell Cardiol 1999;31:2101–2114.
61.
Kataoka H, Kume N, Miyamoto S, et al: Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions. Circulation 1999;99:3110–3117.
62.
Moriwaki H, Kume N, Kataoka H, et al: Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: Upregulated expression by TNF-alpha. FEBS Lett 1998;440:29–32.
63.
Kume N, Moriwaki H, Kataoka H, et al: Inducible expression of LOX-1, a novel receptor for oxidized LDL, in macrophages and vascular smooth muscle cells. Ann NY Acad Sci 2000;902:323–327.
64.
Chen M, Kakutani M, Minami M, et al: Increased expression of lectin-like oxidized low density lipoprotein receptor-1 in initial atherosclerotic lesions of Watanabe heritable hyperlipidemic rabbits. Arterioscler Thromb Vasc Biol 2000;20:1107–1115.
65.
Cominacini L, Pasini AF, Garbin U, et al: Oxidized low density lipoprotein (ox-LDL) binding to ox-LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increased production of intracellular reactive oxygen species. J Biol Chem 2000;275:12633–12638.
66.
Li D, Mehta JL: Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation 2000;101:2889–2895.
67.
Shimaoka T, Kume N, Minami M, et al: Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) supports cell adhesion to fibronectin. FEBS Lett 2001;504:65–68.
68.
Shimaoka T, Kume N, Minami M, et al: LOX-1 supports adhesion of gram-positive and gram-negative bacteria. J Immunol 2001;166:5108–5114.
69.
Price DT, Loscalzo J: Cellular adhesion molecules and atherogenesis. Am J Med 1999;107:85–97.
70.
Albelda SM, Buck CA: Integrins and other cell adhesion molecules. FASEB J 1990;4:2868–2880.
71.
Dustin ML, Rothlein R, Bhan AK, Dinarello CA, Springer TA: Induction by IL 1 and interferon-gamma: Tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol 1986;137:245–254.
72.
Pober JS, Gimbrone MAJ, Lapierre LA, et al: Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 1986;137:1893–1896.
73.
DeLisser HM, Chilkotowsky J, Yan HC, Daise ML, Buck CA, Albelda SM: Deletions in the cytoplasmic domain of platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31) result in changes in ligand binding properties. J Cell Biol 1994;124:195–203.
74.
Romer LH, McLean NV, Yan HC, Daise M, Sun J, DeLisser HM: IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells. J Immunol 1995;154:6582–6592.
75.
McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF: GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989;84:92–99.
76.
Bevilacqua MP, Pober JS, Wheeler ME, Cotran RS, Gimbrone MAJ: Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest 1985;76:2003–2011.
77.
Rosen SD: Cell surface lectins in the immune system. Semin Immunol 1993;5:237–247.
78.
Heldin CH, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev 1999;79:1283–1316.
79.
Waltenberger J: Modulation of growth factor action: Implications for the treatment of cardiovascular diseases. Circulation 1997;96:4083–4094.
80.
Claesson-Welsh L, Eriksson A, Westermark B, Heldin CH: cDNA cloning and expression of the human A-type platelet-derived growth factor (PDGF) receptor establishes structural similarity to the B-type PDGF receptor. Proc Natl Acad Sci USA 1989;86:4917–4921.
81.
Claesson-Welsh L, Eriksson A, Westermark B, Heldin CH: Cloning and expression of human platelet-derived growth factor alpha and beta receptors. Methods Enzymol 1991;198:72–77.
82.
Heldin CH, Ostman A, Eriksson A, Siegbahn A, Claesson-Welsh L, Westermark B: Platelet-derived growth factor: Isoform-specific signalling via heterodimeric or homodimeric receptor complexes. Kidney Int 1992;41:571–574.
83.
Siegbahn A, Hammacher A, Westermark B, Heldin CH: Differential effects of the various isoforms of platelet-derived growth factor on chemotaxis of fibroblasts, monocytes, and granulocytes. J Clin Invest 1990;85:916–920.
84.
Lindner V, Reidy MA: Platelet-derived growth factor ligand and receptor expression by large vessel endothelium in vivo. Am J Pathol 1995;146:1488–1497.
85.
Jawien A, Bowen-Pope DF, Lindner V, Schwartz SM, Clowes AW: Platelet-derived growth factor promotes smooth muscle migration and intimal thickening in a rat model of balloon angioplasty. J Clin Invest 1992;89:507–511.
86.
Ferns GA, Raines EW, Sprugel KH, Motani AS, Reidy MA, Ross R: Inhibition of neointimal smooth muscle accumulation after angioplasty by an antibody to PDGF. Science 1991;253:1129–1132.
87.
Banai S, Wolf Y, Golomb G, et al: PDGF-receptor tyrosine kinase blocker AG1295 selectively attenuates smooth muscle cell growth in vitro and reduces neointimal formation after balloon angioplasty in swine. Circulation 1998;97:1960–1969.
88.
Billett MA, Adbeish IS, Alrokayan SA, Bennett AJ, Marenah CB, White DA: Increased expression of genes for platelet-derived growth factor in circulating mononuclear cells of hypercholesterolemic patients. Arterioscler Thromb Vasc Biol 1996;16:399–406.
89.
Rutherford C, Martin W, Carrier M, Anggard EE, Ferns GA: Endogenously elicited antibodies to platelet derived growth factor-BB and platelet cytosolic protein inhibit aortic lesion development in the cholesterol-fed rabbit. Int J Exp Pathol 1997;78:21–32.
90.
Brown DM, Hong SP, Farrell CL, Pierce GF, Khouri RK: Platelet-derived growth factor BB induces functional vascular anastomoses in vivo. Proc Natl Acad Sci USA 1995;92:5920–5924.
91.
Edelman ER, Nugent MA, Smith LT, Karnovsky MJ: Basic fibroblast growth factor enhances the coupling of intimal hyperplasia and proliferation of vasa vasorum in injured rat arteries. J Clin Invest 1992;89:465–473.
92.
Neschis DG, Safford SD, Hanna AK, Fox JC, Golden MA: Antisense basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model. J Vasc Surg 1998;27:126–134.
93.
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.
94.
Stavri GT, Zachary IC, Baskerville PA, Martin JF, Erusalimsky JD: Basic fibroblast growth factor upregulates the expression of vascular endothelial growth factor in vascular smooth muscle cells: Synergistic interaction with hypoxia. Circulation 1995;92:11–14.
95.
Horrigan MC, MacIsaac AI, Nicolini FA, et al: Reduction in myocardial infarct size by basic fibroblast growth factor after temporary coronary occlusion in a canine model. Circulation 1996;94:1927–1933.
96.
Hiltunen MO, Laitinen M, Turunen MP, et al: Intravascular adenovirus-mediated VEGF-C gene transfer reduces neointima formation in balloon-denuded rabbit aorta. Circulation 2000;102:2262–2268.
97.
Bräsen JH, Kivelä A, Röser K, et al: Angiogenesis, VEGF and PDGF-BB expression, iron deposition and oxidation-specific epitopes in stented human coronary arteries. Arterioscler Thromb Vasc Biol 2001;21:1720–1726.
98.
Tsunawaki S, Sporn M, Ding A, Nathan C: Deactivation of macrophages by transforming growth factor-beta. Nature 1988;334:260–262.
99.
Falcone DJ, McCaffrey TA, Haimovitz-Friedman A, Garcia M: Transforming growth factor-beta 1 stimulates macrophage urokinase expression and release of matrix-bound basic fibroblast growth factor. J Cell Physiol 1993;155:595–605.
100.
Björkerud S: Effects of transforming growth factor-beta 1 on human arterial smooth muscle cells in vitro. Arterioscler Thromb 1991;11:892–902.
101.
Battegay EJ, Raines EW, Seifert RA, Bowen-Pope DF, Ross R: TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop. Cell 1990;63:515–524.
102.
Rasmussen LM, Wolf YG, Ruoslahti E: Vascular smooth muscle cells from injured rat aortas display elevated matrix production associated with transforming growth factor-beta activity. Am J Pathol 1995;147:1041–1048.
103.
Heimark RL, Twardzik DR, Schwartz SM: Inhibition of endothelial regeneration by type-beta transforming growth factor from platelets. Science 1986;233:1078–1080.
104.
Bell L, Madri JA: Effect of platelet factors on migration of cultured bovine aortic endothelial and smooth muscle cells. Circ Res 1989;65:1057–1065.
105.
Chen JK, Hoshi H, McKeehan WL: Transforming growth factor type beta specifically stimulates synthesis of proteoglycan in human adult arterial smooth muscle cells. Proc Natl Acad Sci USA 1987;84:5287–5291.
106.
Kanzaki T, Tamura K, Takahashi K, et al: In vivo effect of TGF-beta 1: Enhanced intimal thickening by administration of TGF- beta 1 in rabbit arteries injured with a balloon catheter. Arterioscler Thromb Vasc Biol 1995;15:1951–1957.
107.
Wolf YG, Rasmussen LM, Ruoslahti E: Antibodies against transforming growth factor-beta 1 suppress intimal hyperplasia in a rat model. J Clin Invest 1994;93:1172–1178.
108.
Bobik A, Agrotis A, Kanellakis P, et al: Distinct patterns of transforming growth factor-beta isoform and receptor expression in human atherosclerotic lesions: Colocalization implicates TGF-beta in fibrofatty lesion development. Circulation 1999;99:2883–2891.
109.
McCaffrey TA, Du B, Fu C, et al: The expression of TGF-beta receptors in human atherosclerosis: Evidence for acquired resistance to apoptosis due to receptor imbalance. J Mol Cell Cardiol 1999;31:1627–1642.
110.
Nikol S, Isner JM, Pickering JG, Kearney M, Leclerc G, Weir L: Expression of transforming growth factor-beta 1 is increased in human vascular restenosis lesions. J Clin Invest 1992;90:1582–1592.
111.
Hariri RJ, Alonso DR, Hajjar DP, Coletti D, Weksler ME: Aging and arteriosclerosis. I. Development of myointimal hyperplasia after endothelial injury. J Exp Med 1986;164:1171–1178.
112.
Hariri RJ, Hajjar DP, Coletti D, Alonso DR, Weksler ME, Rabellino E: Aging and arteriosclerosis: Cell cycle kinetics of young and old arterial smooth muscle cells. Am J Pathol 1988;131:132–136.
113.
McCaffrey TA, Falcone DJ: Evidence for an age-related dysfunction in the antiproliferative response to transforming growth factor-beta in vascular smooth muscle cells. Mol Biol Cell 1993;4:315–322.
114.
McCaffrey TA, Consigli S, Du B, et al: Decreased type II/type I TGF-beta receptor ratio in cells derived from human atherosclerotic lesions: Conversion from an antiproliferative to profibrotic response to TGF-beta1. J Clin Invest 1995;96:2667–2675.
115.
McCaffrey TA, Du B, Consigli S, et al: Genomic instability in the type II TGF-beta1 receptor gene in atherosclerotic and restenotic vascular cells. J Clin Invest 1997;100:2182–2188.
116.
Topouzis S, Majesky MW: Smooth muscle lineage diversity in the chick embryo: Two types of aortic smooth muscle cell differ in growth and receptor-mediated transcriptional responses to transforming growth factor-beta. Dev Biol 1996;178:430–445.
117.
Tedgui A, Mallat Z: Anti-inflammatory mechanisms in the vascular wall. Circ Res 2001;88:877–887.
118.
Brod SA: Unregulated inflammation shortens human functional longevity. Inflamm Res 2001;49:561–570.
119.
Sarkar R, Webb RC: Does nitric oxide regulate smooth muscle cell proliferation? A critical appraisal. J Vasc Res 1998;35:135–142.
120.
Murdoch C, Finn A: Chemokine receptors and their role in inflammation and infectious diseases. Blood 2000;95:3032–3043.
121.
Gerszten RE, Mach F, Sauty A, Rosenzweig A, Luster AD: Chemokines, leukocytes, and atherosclerosis. J Lab Clin Med 2000;136:87–92.
122.
Nelken NA, Coughlin SR, Gordon D, Wilcox JN: Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest 1991;88:1121–1127.
123.
Gosling J, Slaymaker S, Gu L, et al: MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 1999;103:773–778.
124.
Gu L, Okada Y, Clinton SK, et al: Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 1998;2:275–281.
125.
Dawson TC, Kuziel WA, Osahar TA, Maeda N: Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 1999;143:205–211.
126.
Boisvert WA, Santiago R, Curtiss LK, Terkeltaub RA: A leukocyte homologue of the IL-8 receptor CXCR-2 mediates the accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice. J Clin Invest 1998;101:353–363.
127.
Chinetti G, Fruchart JC, Staels B: Peroxisome proliferator-activated receptors (PPARs): Nuclear receptors at the crossroads between lipid metabolism and inflammation. Inflamm Res 2000;49:497–505.
128.
Marx N, Sukhova G, Murphy C, Libby P, Plutzky J: Macrophages in human atheroma contain PPARgamma: Differentiation-dependent peroxisomal proliferator-activated receptor gamma (PPARgamma) expression and reduction of MMP-9 activity through PPARgamma activation in mononuclear phagocytes in vitro. Am J Pathol 1998;153:17–23.
129.
Tontonoz P, Nagy L, Alvarez JG, Thomazy VA, Evans RM: PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998;93:241–252.
130.
Marx N, Bourcier T, Sukhova GK, Libby P, Plutzky J: PPARgamma activation in human endothelial cells increases plasminogen activator inhibitor type-1 expression: PPARgamma as a potential mediator in vascular disease. Arterioscler Thromb Vasc Biol 1999;19:546–551.
131.
Huang JT, Welch JS, Ricote M, et al: Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 1999;400:378–382.
132.
Tanaka T, Itoh H, Doi K, et al: Downregulation of peroxisome proliferator-activated receptor gamma expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia 1999;42:702–710.
133.
Forman BM, Chen J, Evans RM: Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci USA 1997;94:4312–4317.
134.
Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM: 15-Deoxy-delta 12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995;83:803–812.
135.
Delerive P, Furman C, Teissier E, Fruchart J, Duriez P, Staels B: Oxidized phospholipids activate PPARalpha in a phospholipase A2-dependent manner. FEBS Lett 2000;471:34–38.
136.
Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM: A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 1995;83:813–819.
137.
Kliewer SA, Sundseth SS, Jones SA, et al: Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 1997;94:4318–4323.
138.
Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995;270:12953–12956.
139.
Martin G, Schoonjans K, Lefebvre AM, Staels B, Auwerx J: Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARalpha and PPARgamma activators. J Biol Chem 1997;272:28210–28217.
140.
Schoonjans K, Staels B, Auwerx J: The peroxisome proliferator activated receptors (PPARS) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1996;1302:93–109.
141.
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK: The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998;391:79–82.
142.
Frick MH, Syvanne M, Nieminen MS, et al: Prevention of the angiographic progression of coronary and vein-graft atherosclerosis by gemfibrozil after coronary bypass surgery in men with low levels of HDL cholesterol. Lopid Coronary Angiography Trial (LOCAT) Study Group. Circulation 1997;96:2137–2143.
143.
Law RE, Meehan WP, Xi XP, et al: Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest 1996;98:1897–1905.
144.
Collins T, Cybulsky MI: NF-kappaB: Pivotal mediator or innocent bystander in atherogenesis? J Clin Invest 2001;107:255–264.
145.
Viita H, Ylä-Herttuala S: Effects of lipoxygenases on gene expression in mammalian cells; in Sen CK, Sies H, Baeuerle PA (eds): Antioxidant and Redox Regulation of Genes. San Diego, Academic Press, 2000, pp 339–358.
146.
Brand K, Eisele T, Kreusel U, et al: Dysregulation of monocytic nuclear factor-kappa B by oxidized low-density lipoprotein. Arterioscler Thromb Vasc Biol 1997;17:1901–1909.
147.
Pueyo ME, Gonzalez W, Nicoletti A, Savoie F, Arnal JF, Michel JB: Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 2000;20:645–651.
148.
Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI: The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 2000;97:9052–9057.
149.
Iiyama K, Hajra L, Iiyama M, et al: Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 1999;85:199–207.
150.
Walsh K, Smith RC, Kim HS: Vascular cell apoptosis in remodeling, restenosis, and plaque rupture. Circ Res 2000;87:184–188.
151.
Rossig L, Dimmeler S, Zeiher AM: Apoptosis in the vascular wall and atherosclerosis. Basic Res Cardiol 2001;96:11–22.
152.
Tricot O, Mallat Z, Heymes C, Belmin J, Leseche G, Tedgui A: Relation between endothelial cell apoptosis and blood flow direction in human atherosclerotic plaques. Circulation 2000;101:2450–2453.
153.
Farb A, Burke AP, Tang AL, et al: Coronary plaque erosion without rupture into a lipid core: A frequent cause of coronary thrombosis in sudden coronary death. Circulation 1996;93:1354–1363.
154.
Mallat Z, Benamer H, Hugel B, et al: Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000;101:841–843.
155.
Iwashina M, Shichiri M, Marumo F, Hirata Y: Transfection of inducible nitric oxide synthase gene causes apoptosis in vascular smooth muscle cells. Circulation 1998;98:1212–1218.
156.
Pollman MJ, Hall JL, Mann MJ, Zhang L, Gibbons GH: Inhibition of neointimal cell bcl-x expression induces apoptosis and regression of vascular disease. Nat Med 1998;4:222–227.
157.
George SJ: Tissue inhibitors of metalloproteinases and metalloproteinases in atherosclerosis. Curr Opin Lipidol 1998;9:413–423.
158.
Baker AH, Zaltsman AB, George SJ, Newby AC: Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro: TIMP-3 promotes apoptosis. J Clin Invest 1998;101:1478–1487.
159.
Ye S, Humphries S, Henney A: Matrix metalloproteinases: Implication in vascular matrix remodelling during atherogenesis. Clin Sci (Colch) 1998;94:103–110.
160.
Galis ZS, Muszynski M, Sukhova GK, et al: Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994;75:181–189.
161.
Fabunmi RP, Baker AH, Murray EJ, Booth RF, Newby AC: Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, -2, and -3 in rabbit aortic smooth muscle cells. Biochem J 1996;315:335–342.
162.
Lee E, Grodzinsky AJ, Libby P, Clinton SK, Lark MW, Lee RT: Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture. Arterioscler Thromb Vasc Biol 1995;15:2284–2289.
163.
Shapiro SD, Campbell EJ, Kobayashi DK, Welgus HG: Immune modulation of metalloproteinase production in human macrophages: Selective pretranslational suppression of interstitial collagenase and stromelysin biosynthesis by interferon-gamma. J Clin Invest 1990;86:1204–1210.
164.
Xie B, Dong Z, Fidler IJ: Regulatory mechanisms for the expression of type IV collagenases/gelatinases in murine macrophages. J Immunol 1994;152:3637–3644.
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2002
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