Role of cyclophilin A overexpression in angiotensin II/mechanical stretch-induced vascular remodeling: Protective effect of adiponectin

Abstract

Hypertension is associated with an increase in reactive oxygen species (ROS). Cyclophilin A (CyPA) is released from vascular cells in response to oxidative stress and contributes to hypertension pathophysiology. Thereby, controlling redox imbalance and CyPA secretion may prevent hypertension-associated complications. Moreover, adiponectin (APN), an adipocyte-released cytokine, exerts protective effects on the cardiovascular system. Yet, the molecular mechanisms by which CyPA induces vascular remodeling and the role of APN in preventing CyPA secretion still need to be better understood. In this study, we used three models to mimic hypertension: The in-vivo rat portal vein (RPV) ligation and two ex-vivo models (The mechanically stretched RPVs and the angiotensin II treated rat aortas). Our results revealed plasma CyPA levels significantly increased after RPV ligation for 14 and 28 days. In addition, CyPA protein and mRNA expressions significantly increased in response to mechanical stretch and Ang-II. Furthermore, CyPA increased the wet weight of RPVs while inhibiting AMPK and eNOS phosphorylation/activation. Moreover, the CyPA effects on blood vessels were attenuated by pre-treatment with APN. In conclusion, CyPA is secreted in response to high blood pressure and promotes vascular hypertrophy by inhibiting AMPK and eNOS activities and activating the RhoA/ROCK pathway. On the other hand, APN attenuates the synthesis and release of CyPA induced by Ang-II and mechanical stretch.