Adiponectin Attenuates Cyclophilin A Induced Vascular Remodeling in Response to Mechanical Stretch and Angiotensin‐II

Abstract

Background and aimsThe mechanisms that contribute to the development of hypertension leading to cardiovascular diseases (CVD) have not been fully‐elucidated. Increased vascular pressure is associated with the formation of reactive oxygen species (ROS) in vascular smooth muscle cells. ROS has been related to the secretion of Cyclophlin A (CyPA). Moreover, studies have shown the incorporation of CyPA in CVD. Obesity is associated with decrease in adiponectin (APN) levels. Several studies have revealed that APN preserves the normal physiology of the heart. In this study, we aimed to investigate whether hypertension/mechanical stretch enhances the overexpression of CyPA protein and to explore the molecular mechanisms that mediates stretch‐induced CyPA expression. We will also assess the different possible pathways of CyPA induced vascular remodeling. We will focus on the protective effects of APN and its effects on CyPA protein expression.MethodsRat portal veins (RPV) organ culture with or without stretching along with aorta organ culture with or without angiotensin‐II (Ang‐II) were performed to study CyPA protein expression. CyPA treatment was also done on aorta and RPV. Western blot was used to study the expression of various proteins. Immunohistochemistry was performed to study ROS, CyPA, adiponectin and leptin expressions.ResultsThis study has shown that CyPA expression increases in response to stretch in RPV and Ang‐II in aorta. Moreover, CyPA was able to increase extracellular signal‐regulated kinases 1/2 (ERK1/2) activation and to decrease 5′‐AMP‐activated protein kinase (AMPK) and endothelial nitric oxide synthase (e‐NOS) phosphorylation. CyPA was also able to increase ROS and leptin expression and to attenuate APN expression. Furthermore, we have shown that APN decreases CyPA expression. This study also demonstrated that RhoA/ROCK inhibition with Y‐27632 and ROS inhibition with apocynin inhibits CyPA expression.ConclusionBased on the obtained results, we showed that mechanical stretch and Ang‐II upregulates CyPA protein expression via activation of ROS and RhoA/ROCK pathway. We also demonstrated that CyPA induces vascular remodeling by phosphorylation/activation of ERK 1/2, by inhibition of AMPK and e‐NOS phosphorylation, by activation of leptin and downregulation of adiponectin. Moreover, the protective effect of adiponectin was also studied and we demonstrated that APN anti‐hypertrophic effect was in part due to inhibition of CyPA activity.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.