PPAR𝛿 Activity in Cardiovascular Diseases: A Potential Pharmacological Target

Figure 1

Effects of PPARδ activation on potential targets implicated in cell death, cell proliferation, and inflammation. PPARδ can be activated not selectively by endogenous agonists (EAs), such as several lipids, long-chain fatty acids (LCFAs), and prostacyclin (PGI₂), or synthetic agonists (SAs). PPARδ activation has an antiapoptotic effect reducing reactive oxygen species (ROS), upregulating 14-3-3ε activity and reducing cytochrome c release from mitochondria and subsequent caspase-3 activation. The effect of PPARδ activation on cell proliferation is cell type dependent. It has a proangiogenetic effect in human umbilical endothelial cells (HUVECs), a proproliferative effect in keratinocytes (KCs), while an antiproliferative effect in smooth muscle cells (SMCs) and in cardiac fibroblasts (FBs) with subsequent reduction of heart fibrosis. PPARδ activation in endothelial progenitor cells (EPCs) enhances vasculogenesis. PPARδ has anti-inflammatory effects by reducing cytokines production and molecules implicated in endothelial/leukocyte interactions.