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"Glitazones and Vascular Disease in Clinical Practice"Prof. Gerald Watts (biography)
English - 2004-06-26 - 37 minutes
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Summary :
Despite the beneficial effects of statins and ACE-inhibitors, Cardiovascular (CVS) risk remains high in diabetic patients. Classical markers of CVS risk do not explain all of the risk in Type-2 diabetics. Dr. Gerald Watts examines the effects of glitazones (with established effects on traditional CVS risk factors and diabetes pathogenesis) on CVS non-traditional CVS risk factors, their direct effects on atherogenesis and on thrombosis and fibrinolysis.
Dr. Watts discusses atherogenesis and the non-traditional markers of CVS risk in this presentation, as well as the distribution and putative roles of PPAR-receptors in various tissues.
Evidence of glitazone effects on markers of CVS risk is presented and the potential sites of glitazone action in limiting vascular inflammation, thrombosis risk, and smooth muscle proliferation are discussed.
Copyright © 2004 E-MedHosting.com Inc
Learning objectives :
After viewing this presentation, participants will be able to discuss:
• The distribution of PPAR-receptors and their actions in various tissues.
• The role that PPAR-gamma agonists may play in reducing CVS risk.
• Both broad and specific mechanisms by which this might be accomplished.
• Effect of glitazones on endothelial dysfunction
• Effect of glitazones on coronary blood flow
• Effect of glitazones on non-traditional markes of CVS risk.
Bibliographic references :
Bakris G, Viberti G, Weston WM, Heise M, Porter LE, Freed MI. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens. 2003 Jan;17(1):7-12.
Calnek DS, Mazzella L, Roser S, Roman J, Hart CM. Peroxisome proliferator-activated receptor gamma ligands increase release of nitric oxide from endothelial cells. Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):52-7.
Collins AR, Meehan WP, Kintscher U, Jackson S, Wakino S, Noh G, Palinski W, Hsueh WA, Law RE. Troglitazone inhibits formation of early atherosclerotic lesions in diabetic and nondiabetic low density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2001 Mar;21(3):365-71.
Delerive P, Gervois P, Fruchart JC, Staels B. Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators. J Biol Chem. 2000 Nov 24;275(47):36703-7.
Haffner SM, Greenberg AS, Weston WM, Chen H, Williams K, Freed MI. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002 Aug 6;106(6):679-84.
Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation. 2001 Nov 27;104(22):2673-8.
Koshiyama H, Shimono D, Kuwamura N, Minamikawa J, Nakamura Y. Rapid communication: inhibitory effect of pioglitazone on carotid arterial wall thickness in type 2 diabetes. J Clin Endocrinol Metab. 2001 Jul;86(7):3452-6.
Law RE, Meehan WP, Xi XP, Graf K, Wuthrich DA, Coats W, Faxon D, Hsueh WA. Troglitazone inhibits vascular smooth muscle cell growth and intimal hyperplasia. J Clin Invest. 1996 Oct 15;98(8):1897-905.
Law RE, Goetze S, Xi XP, Jackson S, Kawano Y, Demer L, Fishbein MC, Meehan WP, Hsueh WA.Expression and function of PPARgamma in rat and human vascular smooth muscle cells. Circulation. 2000 Mar 21;101(11):1311-8.
Marx N, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, Scharnagl H, Hombach V, Koenig W. Antidiabetic PPAR gamma-activator rosiglitazone reduces MMP-9 serum levels in type 2 diabetic patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):283-8.
Marx N, Imhof A, Froehlich J, Siam L, Ittner J, Wierse G, Schmidt A, Maerz W, Hombach V, Koenig W. Effect of rosiglitazone treatment on soluble CD40L in patients with type 2 diabetes and coronary artery disease. Circulation. 2003 Apr 22;107(15):1954-7. Epub 2003 Apr 14.
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 May;83(5):1818-20.
Mohanty P, Aljada A, Ghanim H, Hofmeyer D, Tripathy D, Syed T, Al-Haddad W, Dhindsa S, Dandona P. Evidence for a potent antiinflammatory effect of rosiglitazone. J Clin Endocrinol Metab. 2004 Jun;89(6):2728-35.
Satoh N, Ogawa Y, Usui T, Tagami T, Kono S, Uesugi H, Sugiyama H, Sugawara A, Yamada K, Shimatsu A, Kuzuya H, Nakao K. Antiatherogenic effect of pioglitazone in type 2 diabetic patients irrespective of the responsiveness to its antidiabetic effect. Diabetes Care. 2003 Sep;26(9):2493-9.
Takagi T, Akasaka T, Yamamuro A, Honda Y, Hozumi T, Morioka S, Yoshida K. 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 Nov 1;36(5):1529-35.
Wang TD, Chen WJ, Lin JW, Chen MF, Lee YT. Effects of rosiglitazone on endothelial function, C-reactive protein, and components of the metabolic syndrome in nondiabetic patients with the metabolic syndrome. Am J Cardiol. 2004 Feb 1;93(3):362-5.
Yoshimoto T, Naruse M, Shizume H, Naruse K, Tanabe A, Tanaka M, Tago K, Irie K, Muraki T, Demura H, Zardi L. Vasculo-protective effects of insulin sensitizing agent pioglitazone in neointimal thickening and hypertensive vascular hypertrophy. Atherosclerosis. 1999 Aug;145(2):333-40.
Additional References of Interest
Natali A, Baldeweg S, Toschi E, Capaldo B, Barbaro D, Gastaldelli A, Yudkin JS, Ferrannini E. Vascular effects of improving metabolic control with metformin or rosiglitazone in type 2 diabetes. Diabetes Care. 2004 Jun;27(6):1349-57.
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