PPAR Agonists and Cardiovascular Disease in Diabetes
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 card...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2008-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2008/245410 |
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| Summary: | 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, PPAR𝛼 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
PPAR𝛾 agonists, and more recently dual PPAR𝛼/𝛾 coagonists, has been associated with an excess in cardiovascular events,
possibly reflecting unrecognised fluid retention with potent agonists of the
PPAR𝛾 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. |
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| ISSN: | 1687-4757 1687-4765 |