Cyclophilin A (CypA), secreted from vascular smooth muscle cells and inflammatory cells in response to oxidative stress, promotes vascular atherosclerosis and development of carotid stenosis.
Using immunohistochemistry, we showed that REGγ was highly expressed in these plaques, and the result of RNA-seq in Human umbilical vein endothelial cells (HUVECs), led us to explore and indentify that REGγ significantly promoted cyclophilin A (CyPA) expression, which is a proinflammatory and proapoptotic molecule in atherosclerosis progression.
Cyclophilin A plays a pathogenic role in the development and progression of atherosclerosis, which can be assessed by measuring carotid intima-media thickness.
The analysis of classical risk factors for atherosclerosis revealed that patients with hypertension and hypercholesterolemia had significantly enhanced platelet-bound CyPA, whereas diabetes and smoking were not associated with enhanced CyPA-binding to the platelet surface.
Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes.
We hypothesized that the genetic variation at the cyclophilin A gene (PPIA) could affect the risk for developing atherosclerosis and myocardial infarction.
Our data indicate that CyPA has proinflammatory effects on EC and may play an important role in the pathogenesis of inflammatory diseases, such as atherosclerosis.