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(Hypertension. 2004;44:621.)
© 2004 American Heart Association, Inc.

Editorial Commentaries

Peroxisome Proliferator–Activated Receptors Ligands, Oxidative Stress, and Cardiac Fibroblast Extracellular Matrix Turnover

From the Department of Medicine, University of California, San Diego.

Correspondence to Francisco J. Villarreal, MD, PhD, UCSD Medical Center, 200 W Arbor Dr, San Diego, CA 92103-8412. E-mail fvillarr@ucsd.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The development of muscle hypertrophy and the excess deposition of extracellular matrix (ECM) proteins (ie, myocardial fibrosis) frequently accompany pathological cardiac remodeling. Peroxisome proliferator–activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear factor receptor superfamily. Three different PPARs have been identified to date (PPAR, PPARß, and PPAR). PPARs are endogenously activated by ligands such as fatty acids and eicosanoids. PPARs are known to modulate gene expression for pathways involved in fat, lipid and glucose metabolism, inflammation, cell cycle, and immune responses.¹ The genetic manipulation in mice of PPARs can lead to the modulation of cardiac muscle hypertrophy.² The experimental use of PPAR ligands has also demonstrated their capacity to ameliorate myocardial fibrosis.^3,4 However, the effect of PPAR activation on modulating cardiac fibroblast (CF) ECM turnover has not been explored. PPAR can be activated by small molecules such as glitazones and lead to decreases in glucose and lipid serum levels. These properties of glitazones have been used for the treatment of type 2 diabetes patients for which benefits are derived not only from their ability to enhance insulin sensitivity but to ameliorate development of atherosclerosis.¹

Glitazone derivatives such as rosiglitazone have also been shown to reduce myocardial infarct size after coronary artery occlusion–reperfusion.⁵ Evidence of improved contractile function and reduced levels of markers/mediators of inflammation accompanied the reduction in infarct size. Shiomi et al⁶ showed that long-term postmyocardial infarction treatment of mice with pioglitazone led to an amelioration of adverse left ventricular remodeling, improved contractile function, reduced . . . [Full Text of this Article]