PPARγ Inhibits VSMC Proliferation and Migration via Attenuating Oxidative Stress through Upregulating UCP2

Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor. (PPAR gamma) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPAR gamma may regulate VSMCs function. However, it remains unclear whether activation of PPAR gamma can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPAR gamma on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPAR gamma inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPAR gamma activation upregulated UCP2 expression in VSMCs; PPAR gamma inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPAR gamma ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPAR gamma can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPAR gamma may represent a prospective target for the prevention and treatment of IH-associated vascular diseases.