Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease

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Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, α, δ and γ, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARα is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARγ is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARδ is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARα (fibrates) and γ (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

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