PPARδ, a Potential Therapeutic Target for Heart Disease.

ABSTRACT

The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) can transcriptionally regulate target genes. PPARδ exerts essential regulatory functions in the heart, which requires constant energy supply. PPARδ plays a key role in energy metabolism, controlling not only fatty acid (FA) and glucose oxidation, but also redox homeostasis, mitochondrial biogenesis, inflammation, and cardiomyocyte proliferation. PPARδ signaling is impaired in the heart under various pathological conditions, such as pathological cardiac hypertrophy, myocardial ischemia/reperfusion, doxorubicin cardiotoxicity and diabetic cardiomyopathy. PPARδ deficiency in the heart leads to cardiac dysfunction, myocardial lipid accumulation, cardiac hypertrophy/remodeling and heart failure. This article provides an up-today overview of this research area and discusses the role of PPARδ in the heart in light of the complex mechanisms of its transcriptional regulation and its potential as a translatable therapeutic target for the treatment of cardiac disorders.