Peroxisome proliferator-activated receptor alpha and hypertensive heart disease

Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. It is expressed by cardiomyocytes and regulates gene expression of key proteins involved in myocardial lipid and energy metabolism. Accordingly, the activitity of PPARalpha is an important determinant of cardiomyocyte lipid homeostasis and ATP production. Currently, animal and human data suggest that deactivation of PPARalpha may contribute substantially to phenotypic changes that accompany cardiac growth in conditions of pressure overload, and the hypothesis emerges that a compromised PPARalpha activity may participate in the transition from compensated left ventricular hypertrophy to heart failure in hypertensive heart disease. The availability of PPARalpha activators (e.g. fibric acid derivates and statins) must stimulate investigation into the potential cardioprotective actions of these compounds beyond their hypolipidaemic effects and via restoration of PPARalpha activity in the hypertrophied and failing heart.