PPARs: Protectors or Opponents of Myocardial Function?

Abstract

Over 5 million people in the United States suffer from the complications of heart failure (HF), which is a rapidly expanding health complication. Disorders that contribute to HF include ischemic cardiac disease, cardiomyopathies, and hypertension. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family. There are three PPAR isoforms: PPARα, PPARγ, and PPARδ. They can be activated by endogenous ligands, such as fatty acids, as well as by pharmacologic agents. Activators of PPARs are used for treating several metabolic complications, such as diabetes and hyperlipidemia that are directly or indirectly associated with HF. However, some of these drugs have adverse effects that compromise cardiac function. This review article aims to summarize the current basic and clinical research findings of the beneficial or detrimental effects of PPAR biology on myocardial function.

Figure 1

Metabolic regulation by PPARs. The different PPAR isoform regulates fatty acid and lipid metabolism in liver, heart, skeletal muscle, and adipose tissue. Figures were produced using Servier Medical Art (http://www.servier.com/).

Figure 2

Effect of PPAR activation during cardiac dysfunction. Administration of PPAR agonists has generally been found to have beneficial effects on cardiac function during ischemia (with reperfusion), pressure overload induced hypertrophy, and sepsis-induced cardiac dysfunction. However, the role of PPARα activation in ischemia reperfusion (I/R) injury is unclear as both beneficial and detrimental effects have been reported. Figures were produced using Servier Medical Art (http://www.servier.com).

Figure 3

Effect of PPARα activation on cardiac function after I/R. The role of peroxisome proliferator-activated receptor (PPAR) α activation in I/R injury is unclear as both beneficial and detrimental effects have been reported depending on the experimental model and timing of activation.