The Pleiotropic Effects of PPARs on Vascular Cells and Angiogenesis: Implications for Tissue Engineering

Angiogenesis is a complex process in which capillaries are produced from blood vessels that already exists. Endothelial cells (ECs) and endothelial progenitor cells (EPCs) are pivotal for this process and for the maintenance/restorage of the endothelium. Decreased numbers and dysfunction of these cells have been related to growing cardiovascular risks. Peroxisome-proliferator-activated receptor (PPAR) is a large family of nuclear receptors, characterized by three isotypes: α, β and γ. Numerous studies have shown that PPAR activation is involved in the pathology of a wide range of cardiovascular diseases and has a role in endothelial function, thrombosis and inflammation, etc., suggesting that PPAR agonists may be good candidates to treat the cardiovascular disease. However, controversial results exist on whether this nuclear receptor is inductive or depressive in the process of angiogenesis. Herein, this review will provide a detailed discussion of the up-to-date investigation of the role of PPARs in angiogenesis, with particular reference to their effects on angiogenesis-related cells--i.e., ECs, EPCs, vascular smooth-muscle cells (VSMCs), macrophages and endometrial cells--and will discuss the current and potential future applications of PPAR activators.