Cardiovascular disease and PPARdelta: Targeting the risk factors

Muscat, G. E. and Dressel, U. (2005) Cardiovascular disease and PPARdelta: Targeting the risk factors. Current Opinion in Investigational Drugs, 6 9: 887-894.

Author Muscat, G. E.
Dressel, U.
Title Cardiovascular disease and PPARdelta: Targeting the risk factors
Journal name Current Opinion in Investigational Drugs   Check publisher's open access policy
ISSN 1472-4472
Publication date 2005-01-01
Sub-type Article (original research)
Volume 6
Issue 9
Start page 887
End page 894
Total pages 8
Place of publication London, U. K.
Publisher Thomson Scientific
Language eng
Subject C1
321003 Cardiology (incl. Cardiovascular Diseases)
730106 Cardiovascular system and diseases
Abstract Metabolism, in part, is regulated by the peroxisome proliferator-activated receptors (PPARs). The PPARs act as nutritional lipid sensors and three mammalian PPAR subtypes designated PPARalpha (NR1C1), PPARgamma (NR1C3) and PPARdelta (NR1C2) have been identified. This subgroup of nuclear hormone receptors binds DNA and controls gene expression at the nexus of pathways that regulate lipid and glucose homeostasis, energy storage and expenditure in an organ-specific manner. Recent evidence has demonstrated activation of PPARdelta in the major mass peripheral tissue (ie, adipose and skeletal muscle). It enhances glucose tolerance, insulin-stimulated glucose disposal, lipid catabolism, energy expenditure, cholesterol efflux and oxygen consumption. These effects positively influence the blood-lipid profile. Furthermore, PPARdelta activation produces a predominant type I/slow twitch/oxidative muscle fiber phenotype that leads to increased endurance, insulin sensitivity and resistance to obesity. PPARdelta has rapidly emerged as a potential target in the battle against dyslipidemia, insulin insensitivity, type II diabetes and obesity, with therapeutic efficacy in the treatment of cardiovascular disease risk factors. GW-501516 is currently undergoing phase II safety and efficacy trials in human volunteers for the treatment of dyslipidemia. The outcome of these clinical trials are eagerly awaited against a background of conflicting reports about cancer risks in genetically predisposed animal models. This review focuses on the potential pharmacological utility of selective PPARdelta agonists in the context of risk factors associated with metabolic and cardiovascular disease.
Q-Index Code C1

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Created: Wed, 15 Aug 2007, 17:13:59 EST