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PPAR Research
Volume 2008 (2008), Article ID 245410, 12 pages
http://dx.doi.org/10.1155/2008/245410
Review Article

PPAR Agonists and Cardiovascular Disease in Diabetes

JDRF Center for Diabetes Complications, Baker Heart Research Institute, Melbourne, VIC 3004, Australia

Received 18 July 2007; Accepted 4 October 2007

Academic Editor: Brian N. Finck

Copyright © 2008 Anna C. Calkin and Merlin C. Thomas. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Peroxisome proliferators activated receptors (PPARs) are ligand-activated nuclear transcription factors that play important roles in lipid and glucose homeostasis. To the extent that PPAR agonists improve diabetic dyslipidaemia and insulin resistance, these agents have been considered to reduce cardiovascular risk. However, data from murine models suggests that PPAR agonists also have independent anti-atherosclerotic actions, including the suppression of vascular inflammation, oxidative stress, and activation of the renin angiotensin system. Many of these potentially anti-atherosclerotic effects are thought to be mediated by transrepression of nuclear factor-kB, STAT, and activator protein-1 dependent pathways. In recent clinical trials, PPAR 𝛼 agonists have been shown to be effective in the primary prevention of cardiovascular events, while their cardiovascular benefit in patients with established cardiovascular disease remains equivocal. However, the use of PPAR 𝛾 agonists, and more recently dual PPAR 𝛼 / 𝛾 coagonists, has been associated with an excess in cardiovascular events, possibly reflecting unrecognised fluid retention with potent agonists of the PPAR 𝛾 receptor. Newer pan agonists, which retain their anti-atherosclerotic activity without weight gain, may provide one solution to this problem. However, the complex biologic effects of the PPARs may mean that only vascular targeted agents or pure transrepressors will realise the goal of preventing atherosclerotic vascular disease.