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KMID : 0368120070370120599
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Korean Circulation Journal
2007 Volume.37 No. 12 p.599 ~ p.608
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Safety and Efficacy of Peroxisome Proliferator-Activated Receptor-αAgonist for Treating Cardiovascular Disease
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Kang Young-Ran
Kwak Choong-Hwan
Hwang Jin-Yong
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Abstract
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Peroxisome proliferator-activated receptor (PPAR) -α belongs to the nuclear family of ligand-activated transcriptional factors. The main role of PPAR-α is to activate the expression of the genes that are involved in fatty acid oxidation to achieve energy homeostasis. Fibrates are a known class of PPAR-α agonists, and they been used clinically for their effects of lowering triglycerides and elevating high-density lipoprotein-cholesterol (HDL-C). Further, recent experimental studies have demonstrated the anti-inflammatory and anti-atherosclerotic actions of PPAR-α agonists directly on the vascular wall. PPAR agonists are currently emerging as a promising therapeutic option to control systemic and vascular atherogenic factors. Regardless of their strong anti-atherosclerotic properties, large clinical studies have demonstrated inconsistent results for the cardioprotective effect of PPAR-α agonists; moreover, it has been observed that they did not decrease the total mortality, which stands in contrast to the statin trials. This review summarizes the current knowledge regarding the PPAR biology and the mechanisms of the effects of PPAR-α on lipid metabolism, the vessel wall and the cardiac metabolism. We also describe the results and lessons learned from the important clinical trials of PPAR-α agonists and we discuss these drugs’ efficacy and safety
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KEYWORD
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PPAR-α, Fibrates, Safety
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