Peroxisome proliferator-activated receptors (PPARs) and their role in the vessel wall: Possible mediators of cardiovascular risk?

European Journal of Cardiovascular Prevention & Rehabilitation

Volumn 8, Issue 4, 2001, Pages 203-210

  Marx, Nikolaus ^a   Libby, Peter ^b   Plutzky, Jorge ^b  

^a UNIVERSITY OF ULM   (Germany)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Atherogenesis; Inflammation; PPARs; Vasculature

Indexed keywords

2,4 THIAZOLIDINEDIONE; FIBRIC ACID DERIVATIVE; LIGAND; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

ATHEROGENESIS; ATHEROSCLEROSIS; BLOOD VESSEL WALL; CARDIOVASCULAR RISK; FATTY ACID OXIDATION; GENE EXPRESSION REGULATION; HUMAN; INFLAMMATION; LIPID METABOLISM; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW;

ARTERIOSCLEROSIS; HUMANS; LIPID METABOLISM; MUSCLE, SMOOTH, VASCULAR; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRANSCRIPTION FACTORS; VASCULAR CELL ADHESION MOLECULE-1;

EID: 0034878539     PISSN: 17418267     EISSN: 17418275     Source Type: Journal    
DOI: 10.1177/174182670100800404     Document Type: Article

References (74)

1. Schoonjans K, Martin G, Staels B, Auwerx J. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol 1997; 8: 159–166.
2. 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.
3. 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.
4. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS, 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.
5. Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998; 98: 2088–2093.
6. Auboeuf D, Rieusset J, Fajas L, Vallier P, Frering V, Riou JP, et al Tissue distribution and quantification of the expression of mRNAs of peroxisome proliferator-activated receptors and liver X receptor-alpha in humans: No alteration in adipose tissue of obese and NIDDM patients. Diabetes 1997; 46: 1319–1327.
7. Lee SS, Pineau T, Drago J, Lee EJ, Owens JW, Kroetz DL, et al Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995; 15: 3012–3022.
8. Peters JM, Cattley RC, Gonzalez FJ. Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis 1997; 18: 2029–2033.
9. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid- activated transcription factor. Cell 1994; 79: 1147–1156.
10. Fajas L, Fruchart JC, Auwerx J. Transcriptional control of adipogenesis. Curr Opin Cell Biol 1998; 10: 165–173.
11. Wu Z, Xie Y, Bucher NL, Farmer SR. Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev 1995; 9: 2350–2363.
12. Yeh WC, Cao Z, Classon M, McKnight SL. Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. Genes Dev 1995; 9: 168–181.
13. 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.
14. Nagy L, Tontonoz P, Alvarez JG, Chen H, Evans RM. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARgamma. Cell 1998; 93: 229–240.
15. 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.
16. Schoonjans K, Auwerx J. Thiazoledinediones: An update. The Lancet 2000; 355: 1008–1010.
17. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, Karin M, Santoro M.G., Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinase. Nature 2000; 403: 103–108.
18. Auwerx J. PPARgamma, the ultimate thrifty gene. Diabetologia 1999; 42: 1033–1049.
19. Ristow M, Muller Wieland D, Pfeiffer A, Krone W, Kahn CR. Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 1998; 339: 953–959.
20. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, et al A Pro 12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998; 20: 284–287.
21. Kubota N, Terauchi Y, Miki H, Tamemoto H, Yamauchi T, Komeda K, et al PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 1999; 4: 597–609.
22. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312.
23. Marx N, Schönbeck U, Lazar MA, Libby P, Plutzky J. Peroxisome proliferator activated receptor gamma activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998; 83: 1097–1103.
24. Staels B, Koenig W, Habib A, Merval R, Lebret M, Torra IP, et al Activation of human aortic smooth-muscle cells is inhibited by PPARalpha but not by PPARgamma activators. Nature 1998; 393: 790–793.
25. Inoue I, Shino K, Noji S, Awata T, Katayama S. Expression of peroxisome proliferator-activated receptor alpha (PPAR alpha) in primary cultures of human vascular endothelial cells. Biochem Biophys Res Commun 1998; 246: 370–374.
26. Marx N, Sukhova G, Collins T, Libby P, Plutzky J. PPARα activators inhibit cytokine-induced vascular cell adhesion molecule 1 expression in human endothelial cells. Circulation 1999; 99: 3125–3131.
27. Chinetti G, Griglio S, Antonucci M, Torra IP, Delerive P, Majd Z, et al Activation of proliferator-activated receptors alpha and gamma induces apoptosis of human monocyte-derived macrophages. J Biol Chem 1998; 273: 25573–25580.
28. Marx N, Mackman N, Schönbeck U, Yilmaz N, Hombach V, Libby P, et al PPARalpha activators inhibit Tissue Factor expression and activity in human monocytes. Circulation 2001; 103: 213–219.
29. Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, et al Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 1999; 274: 32048–32054.
30. Nawa T, Nawa MT, Cai Y, Zhang C, Uchimura I, Narumi S, et al Repression of TNF-alpha-induced E-selectin expression by PPAR activators: Involvement of transcriptional repressor LRF/ATF3. Biochem Biophys Res Commun 2000; 275: 406–411.
31. Delerive P, Martin-Nizard F, Chinetti G, Trottein F, Fruchart JC, Najib J, et al Peroxisome proliferator-activated receptor activators inhibit thrombin-induced endothelin-1 production in human vascular endothelial cells by inhibiting the activator protein-1 signaling pathway. Circ Res 1999; 85: 394–402.
32. 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.
33. Lee H, Shi W, Tontonoz P, Wang S, Subbanagounder G, Hedrick CC, et al Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 2000; 87: 516–521.
34. Neve BP, Corseaux D, Chinetti G, Zawadzki C, Fruchart JC, Duriez P, et al PPARalpha agonists inhibit tissue factor expression in human monocytes and macrophages. Circulation 2001; 103: 207–212.
35. 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.
36. Jiang C, Ting AT, Seed B. PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 82–86.
37. 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.
38. Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J, et al Expression of the peroxisome proliferator-activated receptor gamma (PPARgamma) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 1998; 95: 7614–7619.
39. 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.
40. Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L, et al Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation 2000; 101: 1311–1318.
41. Law RE, Meehan WP, Xi XP, Graf K, Wuthrich DA, Coats W, et al Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest 1996; 98: 1897–1905.
42. Goetze S, Xi XP, Kawano H, Gotlibowski T, Fleck E, Hsueh WA, et al PPAR gamma-ligands inhibit migration mediated by multiple chemoattractants in vascular smooth muscle cells. J Cardiovasc Pharmacol 1999; 33: 798–806.
43. Goetze S, Xi XP, Kawano Y, Kawano H, Fleck E, Hsueh WA, et al TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent. Hypertension 1999; 33: 183–189.
44. Hattori Y, Hattori S, Kasai K. Troglitazone upregulates nitric oxide synthesis in vascular smooth muscle cells. Hypertension 1999; 33: 943–948.
45. Takeda K, Ichiki T, Tokunou T, Funakoshi Y, Iino N, Hirano K, et al Peroxisome proliferator-activated receptor activators downregulate angiotensin II Type 1 receptor in vascular smooth muscle cells. Circulation 2000; 102: 1834–1839.
46. Li M, Pascual G, Glass CK. Peroxisome proliferator-activated receptor gamma-dependent repression of the inducible nitric oxide synthase gene. Mol Cell Biol 2000; 20: 4699–4707.
47. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999; 274: 9116–9121.
48. Satoh H, Tsukamoto K, Hashimoto Y, Hashimoto N, Togo M, Hara M, et al Thiazolidinediones suppress endothelin-1 secretion from bovine vascular endothelial cells: A new possible role of PPARgamma on vascular endothelial function. Biochem Biophys Res Commun 1999; 254: 757–763.
49. Pasceri V, Wu HD, Willerson JT, Yeh ET. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 2000; 101: 235–238.
50. Marx N, Mach F, Sauty A, Sarafi M, Libby P, Plutzky J, et al PPARƔ activators inhibit Interferon-gamma-induced expression of the T cell-active CXC chemokines IP-10, Mig, and I-TAC in human endothelial cells. J Immunol 2000; 164: 6503–6508.
51. Loskutoff DJ, Samad F. The adipocyte and hemostatic balance in obesity: Studies of PAI-1. Arterioscler Thromb Vasc Biol 1998; 18: 1–6.
52. Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, et al Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction. Lancet 1987; 2: 3–9.
53. Kato K, Satoh H, Endo Y, Yamada D, Midorikawa S, Sato W, et al Thiazolidinediones down-regulate plasminogen activator inhibitor type 1 expression in human vascular endothelial cells: A possible role for PPARgamma in endothelial function. Biochem Biophys Res Commun 1999; 258: 431–435.
54. Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL, et al Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82: 2108–2116.
55. 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.
56. Li AC, Brown KK, Silvestre MJ, Willson TM, Palinski W, Glass CK. Peroxisome proliferator-activated receptor gamma ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2000; 106: 523–531.
57. Chinetti G, Lestavel S, Bocher V, Remaley AT, Neve B, Torra IP, et al PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7: 53–58.
58. Moore KJ, Rosen ED, Fitzgerald ML, Randow F, Andersson LP, Altshuler D, et al The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Nat Med 2001; 7: 41–47.
59. Chawla A, Barak Y, Nagy L, Liao D, Tontonoz P, Evans RM. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 2001; 7: 48–52.
60. Kromhout D, Bosschieter EB, de Lezenne Coulander C. The inverse relation between fish consumption and 20-year mortality from coronary heart disease. N Engl J Med 1985; 312: 1205–1209.
61. Harker LA, Kelly AB, Hanson SR, Krupski W, Bass A, Osterud B, et al Interruption of vascular thrombus formation and vascular lesion formation by dietary n-3 fatty acids in fish oil in nonhuman primates. Circulation 1993; 87: 1017–1029.
62. Hahmann HW, Bunte T, Hellwig N, Hau U, Becker D, Dyckmans J, et al Progression and regression of minor coronary arterial narrowings by quantitative angiography after fenofibrate therapy. Am J Cardiol 1991; 67: 957–961.
63. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med 1999; 341: 410–418.
64. Minamikawa J, Tanaka S, Yamauchi M, Inoue D, Koshiyama H. Potent inhibitory effect of troglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab 1998; 83: 1818–1820.
65. Murakami T, Mizuno S, Ohsato K, Moriuchi I, Arai Y, Nio Y, et al Effects of troglitazone on frequency of coronary vasospastic-induced angina pectoris in patients with diabetes mellitus. Am J Cardiol 1999; 84: 92–94.
66. Takagi T, Akasaka T, Yamamuro A, Honda Y, Hozumi T, Morioka S, et al Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus: A serial intravascular ultrasound study. J Am Coll Cardiol 2000; 36: 1529–1535.
67. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, et al Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension [see comments]. Nature 1999; 402: 880–883.
68. Plosker GL, Faulds D. Troglitazone: A review of its use in the management of type 2 diabetes mellitus. Drugs 1999; 57: 409–438.
69. Xin X, Yang S, Kowalski J, Gerritsen ME. Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 1999; 274: 9116–9121.
70. Lazar MA. Progress in cardiovascular biology: PPAR for the course. Nat Med 2001; 7: 23–24.
71. Rosen ED, Spiegelman BM. Peroxisome proliferator-activated receptor gamma ligands and atherosclerosis: Ending the heartache. J Clin Invest 2000; 106: 629–631.
72. Ihara H, Urano T, Takada A, Loskutoff DJ. Induction of plasminogen activator inhibitor-1 (PAI-1) gene expression in adipocytes by thiazolidinediones. Faeb J 2001; 5: 5.
73. Chen Z, Ishibashi S, Perrey S, Osuga J, Gotoda T, Kitamine T, et al Troglitazone inhibits atherosclerosis in apolipoprotein R-knockout mice: Pleiotropic effects on CD36 expression and HDL. Arterioscler Thromn Vasc Biol 2001; 21: 372–377.
74. Collins AR, Meehan WP, Kintscher U, Jackson S, Wakino S, Noh G, et al Toglitazone inhibits formation of early atheroscleorotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice. Arteioscler Thromb Vasc Biol 2001; 21: 365–371.