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Peroxisome Proliferator-Activated Receptor-β and its Agonists in Hypertension and Atherosclerosis

Mechanisms and Clinical Implications

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Abstract

Cardiovascular diseases are the leading cause of morbidity and mortality in the US. Proper management and/ or prevention of atherosclerosis and hypertension, two complex and chronic disorders, would significantly reduce the risk for cardiovascular events such as myocardial infarction and stroke, but this requires an understanding of the mechanisms underlying their development and progression. Whereas a great deal has been learned and applied toward the management of these disorders, especially hypertension, morbidity and mortality remains unacceptably high, most likely because there are disease-causing mechanisms that have yet to be fully recognized. Understanding these disease mechanisms is necessary so that novel management strategies can be developed. One of these novel mechanisms centers on peroxisome proliferator-activated receptor (PPAR)-β. PPAR-β is a member of the nuclear receptor superfamily of ligand-activated transcription factors known to play a role in glucose homeostasis and adipocyte differentiation and, more recently, has been shown to have anti-inflammatory, antiatherogenic, and antihypertensive effects. Thiazolidinediones, a class of drugs used in the treatment of type 2 diabetes mellitus, are high-affinity ligands for PPAR-β. In this review, the anti-inflammatory, anti-atherosclerotic, and anti-hypertensive mechanisms by which PPAR-β and its agonists are thought to exert protective effects on the cardiovascular system are discussed. Ongoing clinical trials using PPAR-β activators for the management of cardiovascular diseases, especially in patients with type 2 diabetes mellitus, are summarized.

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Acknowledgments

Dr C.D. Sigmund has received grants from the NIH (NS24621 and HL55006). Dr C.M. Halabi has received funding from an institutional training grant (NRSA T32 6M08629).

The authors have no conflicts of interest that are directly relevant to the content of this review.

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  1. Medical Scientist Training Program and Genetics Program, University of Iowa, Iowa City, Iowa, USA

    Carmen M. Halabi &  Curt D. Sigmund

  2. Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA

    Carmen M. Halabi &  Curt D. Sigmund

  3. Department of Physiology & Biophysics, University of Iowa, Iowa City, Iowa, USA

    Curt D. Sigmund

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Halabi, C.M., Sigmund, C.D. Peroxisome Proliferator-Activated Receptor-β and its Agonists in Hypertension and Atherosclerosis. Am J Cardiovasc Drugs 5, 389–398 (2005). https://doi.org/10.2165/00129784-200505060-00006

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