• 1
    Abbott RD, Donahue RP, Kannel WB, et al. The impact of diabetes on survival following myocardial infarction in men vs women. The Framingham Study. JAMA 1988; 260: 34563460.
  • 2
    Gu K, Cowie CC, Harris MI. Mortality in adults with and without diabetes in a national cohort of the US population, 1971–1993. Diabetes Care 1998; 21: 11381145.
  • 3
    Haffner SM, Lehto S, Ronnemaa T, et al. Mortality from coronary heart disease in subjects with type 2 diabetes and non-diabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339: 229234.
  • 4
    Kannel WB, McGee DL. Diabetes and cardiovascular disease: the Framingham Study. JAMA 1979; 241: 20352038.
  • 5
    Pan WH, Cedres LB, Liu K, et al. Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women. Am J Epidemiol 1986; 123: 504516.
  • 6
    Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977986.
  • 7
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837853.
  • 8
    Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 1995; 28: 103117.
  • 9
    Stettler C, Allemann S, Juni P, et al. Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J 2006; 152: 2738.
  • 10
    Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus: the Finnish Studies. Ann Intern Med 1996; 124: 127130.
  • 11
    Wei M, Gaskill SP, Haffner SM, et al. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. Diabetes Care 1998; 21: 11671173.
  • 12
    Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321: 405412.
  • 13
    Turner RC, Millns H, Neil HA, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS 23). BMJ 1998; 316: 823828.
  • 14
    Pyŏrälä K, Pedersen TR, Kjekshus J, et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care 1997; 20: 614620.
  • 15
    Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet 2003; 361: 20052016.
  • 16
    Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 10011009.
  • 17
    Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation 2000; 102: 18931990.
  • 18
    Sever PS, Dahlöf B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 11491158.
  • 19
    Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685696.
  • 20
    Arampatzis CA, Goedhart D, Serruys PW, et al. Fluvastatin reduces the impact of diabetes on long-term outcome after coronary intervention – a Lescol Intervention Prevention Study (LIPS) substudy. Am Heart J 2005; 149: 329335.
  • 21
    Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998; 351: 17551762.
  • 22
    UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ 1998; 317: 713720.
  • 23
    Niskanen L, Hedner T, Hansson L, et al. Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/beta-blocker-based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care 2001; 24: 20912096.
  • 24
    Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002; 359: 9951003.
  • 25
    Tuomilehto J, Rastenyte D, Birkenhäger WH, et al. Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators. N Engl J Med 1999; 340: 677684.
  • 26
    Spiegelman BM. Peroxisome proliferator-activated receptor γ: a key regulator of adipogenesis and systemic insulin sensitivity. Eur J Med Res 1997; 2: 457464.
  • 27
    Kliewer SA, Lenhard JM, Willson TM, et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation. Cell 1995; 83: 813819.
  • 28
    Desvergne B, Wahli W. Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev 1999; 20: 649688.
  • 29
    Forman BM, Tontonoz P, Chen J, et al. 15-deoxy-Δ12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR-γ. Cell 1995; 83: 803812.
  • 30
    Huang JT, Welch JS, Ricote M, et al. Interleukin-4-dependent production of PPAR-γ ligands in macrophages by 12/15-lipoxygenase. Nature 1999; 400: 378382.
  • 31
    Nagy L, Tontonoz P, Alvarez JG, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPAR-γ. Cell 1998; 93: 229240.
  • 32
    Schopfer FJ, Lin Y, Baker PR, et al. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor γ ligand. Proc Natl Acad Sci USA 2005; 102: 23402345.
  • 33
    Willson TM, Lambert MH, Kliewer SA. Peroxisome proliferator-activated receptor γ and metabolic disease. Annu Rev Biochem 2001; 70: 341367.
  • 34
    Feige JN, Gelman L, Michalik L, et al. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Progr Lipid Res 2006; 45: 120159.
  • 35
    Tolon RM, Castillo AI, Aranda A. Activation of the prolactin protein gene by peroxisome proliferator-activated receptor-alpha appears to be DNA bindingindependent. J Biol Chem 1998; 273: 2665226661.
  • 36
    Ricote M, Li AC, Willson TM, et al. The peroxisome proliferator activated receptor-γ is a negative regulator of macrophage activation. Nature 1998; 391: 7982.
  • 37
    Feinstein DL, Spangolo A, Akar C, et al. Receptor-independent actions of PPAR thiazolidinedione agonists: is a mitochondrial function the key? Biochem Pharm 2005; 70: 177188.
  • 38
    Ricote M, Glass CK. PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta 2007; 1771: 926935.
  • 39
    Diradourian C, Girard J, Pegorier JP. Phosphorylation of PPARs: from molecular characterization to physiological relevance. Biochimie 2005; 87: 3338.
  • 40
    Genini D, Catapano CV. Block of nuclear receptor ubiquitination: a mechanism of ligand-dependent control of peroxisome proliferator-activated receptor δ activity. J Biol Chem 2007; 282: 1177611785.
  • 41
    Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA 1994; 91: 73557359.
  • 42
    Chawla A, Schwarz EJ, Dimaculangan DD, et al. Peroxisome proliferator activated receptor (PPAR) γ: adipose-predominant expression and induction early in adipocyte differentiation. Endocrinology 1994; 135: 798800.
  • 43
    Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-α, -β, and -γ in the adult rat. Endocrinology 1996; 137: 354366.
  • 44
    Jain S, Pulikuri S, Zhu Y, et al. Differential expression of the peroxisome proliferator-activated receptor γ (PPARγ) and its coactivators steroid receptor coactivator-1 and PPAR-binding protein PBP in the brown fat, urinary bladder, colon, and breast of the mouse. Am J Pathol 1998; 153: 349354.
  • 45
    Delerive P, Martin-Nizard F, Chinetti G, 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: 394402.
  • 46
    Marx N, Schonbeck U, Lazar MA, et al. Peroxisome proliferator-activated receptor γ activators inhibit gene expression and migration in human vascular smooth muscle cells. Circ Res 1998; 83: 10971103.
  • 47
    Marx N, Sukhova G, Murphy C, et al. Macrophage in human atheroma contain PPARγ: differentiation-dependent peroxisomal proliferator-activated receptor γ (PPARγ) expression and reduction of MMP-9 activity through PPARγ activation in mononuclear phagocytes in vitro. Am J Pathol 1998; 153: 1723.
  • 48
    Ricote M, Huang J, Fajas L, et al. Expression of the peroxisome proliferator-activated receptor γ (PPARγ) in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci USA 1998; 95: 76147619.
  • 49
    Li AC, Brown KK, Silvestre MJ, et al. Peroxisome proliferator-activated receptor γ ligands inhibit development of atherosclerosis in LDL receptor-deficient mice. J Clin Invest 2000; 106: 523531.
  • 50
    Li AC, Binder CJ, Gutierrez A, et al. Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARα, β/δ, and γ. J Clin Invest 2004; 114: 15641576.
  • 51
    Collins AR, Meehan WP, Kintscher U, et al. Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol 2001; 21: 365371.
  • 52
    Chen Z, Ishibashi S, Perrey S, et al. Troglitazone inhibits atherosclerosis in apolipoprotein E-knockout mice: pleiotropic effects on CD36 expression and HDL. Arterioscler Thromb Vasc Biol 2001; 21: 372377.
  • 53
    Claudel T, Leibowitz MD, Fievet C, et al. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor. Proc Natl Acad Sci USA 2001; 98: 26102615.
  • 54
    Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366: 12791289.
  • 55
    Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 2006; 296: 25722581.
  • 56
    Nissen SE, Nicholls SJ, Wolski K, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 2008; 299: 15611573.
  • 57
    Ogasawara D, Shite J, Shinke T, et al. Pioglitazone reduces the necrotic-core component in coronary plaque in association with enhanced plasma adiponectin in patients with type 2 diabetes mellitus. Circ J 2009; 73: 343351.
  • 58
    Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 24572471.
  • 59
    Singh S, Loke YK, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a meta-analysis. JAMA 2007; 298: 11891195.
  • 60
    Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 2005; 28: 15471554.
  • 61
    Duan SZ, Ivashchenko CY, Russell MW, et al. Cardiomyocyte-specific knockout and agonist of peroxisome proliferator-activated receptor-γ both induce cardiac hypertrophy in mice. Circ Res 2005; 97: 372379.
  • 62
    Jackson SM, Parhami F, Xi XP, et al. Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 1999; 19: 20942104.
  • 63
    Pasceri V, Wu HD, Willerson JT, et al. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-γ activators. Circulation 2000; 101: 235238.
  • 64
    Lee H, Shi W, Tontonoz P, et al. Role of peroxisome proliferator-activated receptor α in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. Circ Res 2000; 87: 516521.
  • 65
    Calnek DS, Mazzella L, Roser S, et al. Peroxisome proliferator-activated receptor γ ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol 2003; 23: 5257.
  • 66
    Wong WT, Tian XY, Xu A, et al. Adiponectin is required for PPARγ-mediated improvement of endothelial function in diabetic mice. Cell Metab 2011; 14: 104115.
  • 67
    Wakino S, Kintscher U, Kim S, et al. Peroxisome proliferator-activated receptor γ ligands inhibit retinoblastoma phosphorylation and G1 [RIGHTWARDS ARROW] S transition in vascular smooth muscle cells. J Biol Chem 2000; 275: 2243522441.
  • 68
    Law RE, Goetze S, Xi XP, et al. Expression and function of PPARγ in rat and human vascular smooth muscle cells. Circulation 2000; 101: 13111318.
  • 69
    Law RE, Meehan WP, Xi XP, et al. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest 1996; 98: 18971905.
  • 70
    Okura T, Nakamura M, Takata Y, et al. Troglitazone induces apoptosis via the p53 and Gadd45 pathway in vascular smooth muscle cells. Eur J Pharmacol 2000; 407: 227235.
  • 71
    Aizawa Y, Kawabe J, Hasebe N, et al. Pioglitazone enhances cytokine-induced apoptosis in vascular smooth muscle cells and reduces intimal hyperplasia. Circulation 2001; 104: 455460.
  • 72
    Takeda K, Ichiki T, Tokunou T, et al. Peroxisome proliferator-activated receptor gamma activators downregulate angiotensin II type 1 receptor in vascular smooth muscle cells. Circulation 2000; 102: 18341839.
  • 73
    Ikeda U, Shimpo M, Murakami Y, et al. Peroxisome proliferator–activated receptor-γ ligands inhibit nitric oxide synthesis in vascular smooth muscle cells. Hypertension 2000; 35: 12321236.
  • 74
    Sugawara A, Takeuchi K, Uruno A, et al. Transcriptional suppression of type 1 angiotensin II receptor gene expression by peroxisome proliferator-activated receptor-γ in vascular smooth muscle cells. Endocrinology 2001; 142: 31253134.
  • 75
    Tham DM, Martin-McNulty B, Wang YX, et al. Angiotensin II is associated with activation of NF-κB-mediated genes and downregulation of PPARs. Physiol Genomics 2002; 11: 2130.
  • 76
    Tontonoz P, Nagy L, Alvarez J, et al. PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 1998; 93: 241252.
  • 77
    Feng J, Han J, Pearce AFA, et al. Induction of CD36 expression by oxidized LDL and IL-4 by a common signaling pathway dependent on protein kinase C and PPARγ. J Lipid Res 2000; 41: 688696.
  • 78
    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: 13331339.
  • 79
    Chawla A, Boisvert WA, Lee CH, et al. A PPARγ–LXR–ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis. Mol Cell 2001; 7: 161171.
  • 80
    Chinetti G, Lestavel S, Bocher V, et al. PPAR-α and PPAR-γ activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway. Nat Med 2001; 7: 5358.
  • 81
    Lawn RM, Wade DP, Garvin MR, et al. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest 1999; 104: R25R31.
  • 82
    Oram JF, Vaughan AM. ABCA1-mediated transport of cellular cholesterol and phospholipids to HDL apolipoproteins. Curr Opin Lipidol 2000; 11: 253260.
  • 83
    Odegaard JI, Ricardo-Gonzalez RR, Goforth MH, et al. Macrophage-specific PPARγ controls alternative activation and improves insulin resistance. Nature 2007; 447: 11161120.
  • 84
    Bouhlel MA, Derudas B, Rigamonti E, et al. PPARγ activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties. Cell Metab 2007; 6: 137143.
  • 85
    Jiang C, Ting AT, Seed B. PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 1998; 391: 8286.
  • 86
    Shu H, Wong B, Zhou G, et al. Activation of PPARα or γ reduces secretion of matrix metalloproteinase 9 but not interleukin 8 from human monocytic THP-1 cells. Biochem Biophys Res Commun 2000; 267: 345349.
  • 87
    Kintscher U, Goetze S, Wakino S, et al. Peroxisome proliferator-activated receptor and retinoid X receptor ligands inhibit monocyte chemotactic protein-1-directed migration of monocytes. Eur J Pharmacol 2000; 401: 259270.
  • 88
    Gordon D, Reidy MA, Benditt EP, et al. Cell proliferation in human coronary arteries. Proc Natl Acad Sci USA 1990; 87: 46004604.
  • 89
    Rosenfeld ME, Ross R. Macrophage and smooth muscle cell proliferation in atherosclerotic lesions of WHHL and comparably hypercholesterolemic fat-fed rabbits. Arteriosclerosis 1990; 10: 680687.
  • 90
    Spagnoli LG, Orlandi A, Santeusanio G. Foam cells of the rabbit atherosclerotic plaque arrested in metaphase by colchicine show a macrophage phenotype. Atherosclerosis 1991; 88: 8792.
  • 91
    Sakai M, Miyazaki A, Hakamata H, et al. Lysophosphatidylcholine plays an essential role in the mitogenic effect of oxidized low density lipoprotein on murine macrophages. J Biol Chem 1994; 269: 3143031435.
  • 92
    Matsumura T, Sakai M, Kobori S, et al. Two intracellular signaling pathways for activation of protein kinase C are involved in oxidized low-density lipoprotein-induced macrophage growth. Arterioscler Thromb Vasc Biol 1997; 17: 30133020.
  • 93
    Martens JS, Reiner NE, Herrera-Velit P, et al. Phosphatidylinositol 3-kinase is involved in the induction of macrophage growth by oxidized low density lipoprotein. J Biol Chem 1998; 273: 49154920.
  • 94
    Hamilton JA, Myers D, Jessup W, et al. Oxidized LDL can induce macrophage survival, DNA synthesis, and enhanced proliferative response to CSF-1 and GM-CSF. Arterioscler Thromb Vasc Biol 1999; 19: 98105.
  • 95
    Yano M, Matsumura T, Senokuchi T, et al. Troglitazone inhibits oxidized low-density lipoprotein-induced macrophage proliferation: impact of the suppression of nuclear translocation of ERK1/2. Atherosclerosis 2007; 191: 2232.
  • 96
    Pascual G, Fong AL, Ogawa S, et al. A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-γ. Nature 2005; 437: 759763.
  • 97
    Ogawa S, Lozach J, Benner C, et al. Molecular determinants of crosstalk between nuclear receptors and toll-like receptors. Cell 2005; 122: 707721.
  • 98
    Saydah SH, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 2004; 291: 335342.
  • 99
    Brown BG, Zhao XQ, Sacco DE, et al. Lipid lowering and plaque regression: new insights into prevention of plaque disruption and clinical events in coronary disease. Circulation 1993; 87: 17811791.
  • 100
    Levine GN, Keaney JFJ, Vita JA. Cholesterol reduction in cardiovascular disease: clinical benefits and possible mechanisms. N Engl J Med 1995; 333: 512521.
  • 101
    Libby P, Aikawa M. New insights in plaque stabilization by lipid lowering. Drugs 1998; 56(suppl 1): 913.
  • 102
    Vaughan CJ, Gotto AMJ, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000; 35: 110.
  • 103
    Goff DC Jr, Gerstein HC, Ginsberg HN, et al. Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007; 99: 4i20i.
  • 104
    American Diabetes Association. Standards of medical care in diabetes-2010. Diabetes Care 2010; 33(Suppl 1): S11S61.
  • 105
    Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. JAMA 1998; 279: 16431650.
  • 106
    Davignon J, Laaksonen R. Low-density lipoprotein-independent effects of statins. Curr Opin Lipidol 1999; 10: 543559.
  • 107
    Corsini A, Bellosta S, Baetta R, et al. New insights into the pharmacodynamic and pharmacokinetic properties of statins. Pharmacol Ther 1999; 84: 413428.
  • 108
    Palinski W. New evidence for beneficial effects of statins unrelated to lipid lowering. Arterioscler Thromb Vasc Biol 2001; 21: 35.
  • 109
    Kwak BR, Mach F. Statins inhibit leukocyte recruitment: new evidence for their anti-inflammatory properties. Arterioscler Thromb Vasc Biol 2001; 21: 12561258.
  • 110
    Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 17121719.
  • 111
    Koh KK. Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability. Cardiovasc Res 2000; 47: 648657.
  • 112
    Grip O, Janciauskiene S, Lindgren S. Atorvastatin activates PPAR-γ and attenuates the inflammatory response in human monocytes. Inflamm Res 2002; 51: 5862.
  • 113
    Zelvyte I, Dominaitiene R, Crisby M, et al. Modulation of inflammatory mediators and PPARγ and NFκB expression by pravastatin in response to lipoproteins in human monocytes in vitro. Pharmacol Res 2002; 45: 147154.
  • 114
    Yano M, Matsumura T, Senokuchi T, et al. Statins activate peroxisome proliferator-activated receptor γ through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages. Circ Res 2007; 100: 14421451.
  • 115
    Degraeve F, Bolla M, Blaie S, et al. Modulation of COX-2 expression by statins in human aortic smooth muscle cells. Involvement of geranylgeranylated proteins. J Biol Chem 2001; 276: 4684946855.
  • 116
    Chen JC, Huang KC, Wingerd B, et al. HMG-CoA reductase inhibitors induce COX-2 gene expression in murine macrophages: role of MAPK cascades and promoter elements for CREB and C/EBPβ. Exp Cell Res 2004; 301: 305319.
  • 117
    Pahan K, Sheikh FG, Namboodiri AM, et al. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. J Clin Invest 1997; 100: 26712679.
  • 118
    Veillard NR, Braunersreuther V, Arnaud C, et al. Simvastatin modulates chemokine and chemokine receptor expression by geranylgeranyl isoprenoid pathway in human endothelial cells and macrophages. Atherosclerosis 2006; 188: 5158.
  • 119
    Argmann CA, Edwards JY, Sawyez CG, et al. Regulation of macrophage cholesterol efflux through hydroxymethylglutaryl-CoA reductase inhibition: a role for RhoA in ABCA1-mediated cholesterol efflux. J Biol Chem 2005; 280: 2221222221.
  • 120
    Strawn WB, Chappell MC, Dean RH, et al. Inhibition of early atherogenesis by losartan in monkeys with dietinduced hypercholesterolemia. Circulation 2000; 101: 15861593.
  • 121
    Hayek T, Attias J, Coleman R, et al. The angiotensin-converting enzyme inhibitor, fosinopril, and the angiotensin II receptor antagonist, losartan, inhibit LDL oxidation and attenuate atherosclerosis independent of lowering blood pressure in apolipoprotein E-deficient mice. Cardiovasc Res 1999; 44: 579587.
  • 122
    Takai S, Kim S, Sakonjo H, et al. Mechanisms of angiotensin II type 1 receptor blocker for anti-atherosclerotic effect in monkeys fed a high-cholesterol diet. J Hypertens 2003; 21: 361369.
  • 123
    Dol F, Martin G, Staels B, et al. Angiotensin AT1 receptor antagonist irbesartan decreases lesion size, chemokine expression, and macrophage accumulation in apolipoprotein E-deficient mice. J Cardiovasc Pharmacol 2001; 38: 395405.
  • 124
    Benson SC, Pershadsingh HA, Ho CI, et al. Identification of telmisartan as a unique angiotensin II receptor antagonist with selective PPARγ-modulating activity. Hypertension 2004; 43: 9931002.
  • 125
    Schupp M, Janke J, Clasen R, et al. Angiotensin type 1 receptor blockers induce peroxisome proliferator-activated receptor-gamma activity. Circulation 2004; 109: 20542057.
  • 126
    Matsumura T, Kinoshita H, Ishii N, et al. Telmisartan exerts anti-atherosclerotic effects by activating PPARγ in macrophages. Arterioscler Thromb Vasc Biol 2011; 31: 12681275.
  • 127
    Takaya T, Kawashima S, Shinohara M, et al. Angiotensin II type 1 receptor blocker telmisartan suppresses superoxide production and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice. Atherosclerosis 2006; 186: 402410.
  • 128
    Blessing E, Preusch M, Kranzhofer R, et al. Anti-atherosclerotic properties of telmisartan in advanced atherosclerotic lesions in apolipoprotein E deficient mice. Atherosclerosis 2008; 199: 295303.
  • 129
    Nagy N, Melchior-Becker A, Fischer JW. Long-term treatment with the AT1-receptor antagonist telmisartan inhibits biglycan accumulation in murine atherosclerosis. Basic Res Cardiol 2010; 105: 2938.
  • 130
    Fukuda D, Enomoto S, Hirata Y, et al. The angiotensin receptor blocker, telmisartan, reduces and stabilizes atherosclerosis in ApoE and AT1aR double deficient mice. Biomed Pharmacother 2010; 64: 712717.
  • 131
    Ikejima H, Imanishi T, Tsujioka H, et al. Effects of telmisartan, a unique angiotensin receptor blocker with selective peroxisome proliferator-activated receptor-γ-modulating activity, on nitric oxide bioavailability and atherosclerotic change. J Hypertens 2008; 26: 964972.
  • 132
    Haraguchi T, Takasarki K, Naito T, et al. Cerebroprotective action of telmisartan by inhibition of macrophages/microglia expressing HMGB1 via a peroxisome proliferator-activated receptor γ-dependent mechanism. Neurosci Lett 2009; 464: 151155.
  • 133
    Iwanami J, Mogi M, Tsukuda K, et al. Low dose of telmisartan prevents ischemic brain damage with peroxisome proliferator-activated receptor-gamma activation in diabetic mice. J Hypertens 2010; 28: 17301737.
  • 134
    Cianchetti S, Del Fiorentino A, Colognato R, et al. Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis 2008; 198: 2228.
  • 135
    Baden T, Yamawaki H, Saito K, et al. Telmisartan inhibits methylglyoxal-mediated cell death in human vascular endothelium. Biochem Biophys Res Commun 2008; 373: 253257.
  • 136
    Bian C, Wu Y, Chen P. Telmisartan increases the permeability of endothelial cells through zonula occludens-1. Biol Pharm Bull 2009; 32: 416420.
  • 137
    Honda A, Matsuura K, Fukushima N, et al. Telmisartan induces proliferation of human endothelial progenitor cells via PPARγ-dependent PI3K/Akt pathway. Atherosclerosis 2009; 205: 376384.
  • 138
    Yamamoto K, Ohishi M, Ho C, et al. Telmisartan-induced inhibition of vascular cell proliferation beyond angiotensin receptor blockade and peroxisome proliferator-activated receptor-γ activation. Hypertension 2009; 54: 13531359.
  • 139
    Imayama I, Ichiki T, Inanaga K, et al. Telmisartan downregulates angiotensin II type 1 receptor through activation of peroxisome proliferator-activated receptor γ. Cardiovasc Res 2006; 72: 184190.
  • 140
    Nakaya K, Ayaori M, Hisada T, et al. Telmisartan enhances cholesterol efflux from THP-1 macrophages by activating PPARγ. J Atheroscler Thromb 2007; 14: 133141.
  • 141
    Pitt B, Byington RP, Furberg CD, et al. Effect of amlodipine on the progression of atherosclerosis and the occurrence of clinical events. PREVENT Investigators. Circulation 2000; 102: 15031510.
  • 142
    Zanchetti A, Bond MG, Hennig M, et al. Calcium antagonist lacidipine slows down progression of asymptomatic carotid atherosclerosis: principal results of the European Lacidipine Study on Atherosclerosis (ELSA), a randomized, double-blind, long-term trial. Circulation 2002; 106: 24222427.
  • 143
    Henry PD, Bentley KI. Suppression of atherogenesis in cholesterol-fed rabbit treated with nifedipine. J Clin Invest 1981; 68: 13661369.
  • 144
    Atkinson JB, Swift LL. Nifedipine reduces atherogenesis in cholesterol-fed heterozygous WHHL rabbits. Atherosclerosis 1990; 84: 195201.
  • 145
    Willis AL, Nagel B, Churchill V, et al. Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits. Atheroslcerosis 1985; 5: 250255.
  • 146
    Lichtlen PR, Hugenholtz PG, Rafflenbeul W, et al. Retardation of angiographic progression of coronary artery disease by nifedipine. Results of the International Nifedipine Trial on Antiatherosclerotic Therapy (INTACT). INTACT Group Investigators. Lancet 1990; 335: 11091113.
  • 147
    Brown MJ, Palmer CR, Castaigne A, et al. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calciumchannel blocker or diuretic in the International Nifedipine GITS study: intervention as a Goal in Hypertension Treatment (INSIGHT). Lancet 2000; 356: 366372.
  • 148
    Motro M, Shemesh J. Calcium channel blocker nifedipine slows down progression of coronary calcification in hypertensive patients compared with diuretics. Hypertension 2001; 37: 14101413.
  • 149
    Simon A, Levenson J. Effects of calcium channel blockers on atherosclerosis: new insights. Acta Cardiol 2002; 57: 249255.
  • 150
    Shinoda E, Yui Y, Kodama K, et al. Quantitative coronary angiogram analysis: nifedipine retard versus angiotensin-converting enzyme inhibitors (JMIC-B side arm study). Hypertension 2005; 45: 11531158.
  • 151
    Ishii N, Matsumura T, Kinoshita H, et al. Nifedipine induces peroxisome proliferator-activated receptor-γ activation in macrophages and suppresses the progression of atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2010; 30: 15981605.
  • 152
    Mulvaney JM, Zhang T, Fewtrell C, et al. Calcium influx through L-type channels is required for selective activation of extracellular signal-regulated kinase by gonadotropin-releasing hormone. J Biol Chem 1999; 274: 2979629804.
  • 153
    Hirata A, Igarashi M, Yamaguchi H, et al. Nifedipine suppresses neointimal thickening by its inhibitory effect on vascular smooth muscle cell growth via a MEK-ERK pathway coupling with Pyk2. Br J Pharmacol 2000; 131: 15211530.
  • 154
    Szabó C, Mitchell JA, Gross SS, et al. Nifedipine inhibits the induction of nitric oxide synthase by bacterial lipopolysaccharide. J Pharmacol Exp Ther 1993; 265: 674680.
  • 155
    Matsumori A, Nishio R, Nose Y. Calcium channel blockers differentially modulate cytokine production by peripheral blood mononuclear cells. Circ J 2010; 74: 567571.
  • 156
    Matsumoria A, Nunokawa Y, Sasayama S. Nifedipine inhibits activation of transcription factor NF-κB. Life Sci 2000; 67: 26552661.
  • 157
    Wu L, Iwai M, Li Z, et al. Nifedipine inhibited angiotensin II-induced monocyte chemoattractant protein 1 expression: involvement of inhibitor of nuclear factor κB kinase and nuclear factor κB-inducing kinase. J Hypertens 2006; 24: 123130.
  • 158
    Suzuki S, Nishimaki-Mogami T, Tamehiro N, et al. Verapamil increases the apolipoprotein-mediated release of cellular cholesterol by induction of ABCA1 expression via liver X receptor-independent mechanism. Arterioscler Thromb Vasc Biol 2004; 24: 519525.
  • 159
    Hashimoto R, Umemoto S, Guo F, et al. Nifedipine activates PPARγ and exerts antioxidative action through Cu/ZnSOD independent of blood-pressure lowering in SHRSP. J Atheroscler Thromb 2010; 17: 785795.
  • 160
    Matsui T, Yamagishi S, Takeuchi M, et al. Nifedipine, a calcium channel blocker, inhibits advanced glycation end product (AGE)-elicited mesangial cell damage by suppressing AGE receptor (RAGE) expression via peroxisome proliferator-activated receptor-γ activation. Biochem Biophys Res Commun 2009; 385: 269272.
  • 161
    Matsui T, Yamagishi S, Takeuchi M, et al. Nifedipine inhibits advanced glycation end products (AGEs) and their receptor (RAGE) interaction-mediated proximal tubular cell injury via peroxisome proliferator-activated receptor-γ activation. Biochem Biophys Res Commun 2010; 398: 326330.
  • 162
    Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011; 34: 916922.