Shear stress-induced MMP1 and PDE2A expressions in coronary atherosclerosis

Abstract

AIM: Biomechanical stress plays an essential role in coronary atherosclerosis (CAS), however, inter-relations between mechanical conditions and gene expressions remain unclear. METHODS: We constructed finite element model of CAS to map human wall shear stress (WSS). Biopsy aortic tissue samples were obtained from 3 CAS patients. Gene expression pattern in CAS was analyzed by GEO datasets. Immunofluorescence staining and western blot confirmed protein expression and localization. RESULTS: Peak WSS was significantly increased in the vessel stenosis of CAS at 0.25 s (mean 55.1 Pa). Analyses results of GSE76275 showed matrix metalloproteinases1 (MMP1) and phosphodiesterase-2A (PDE2A) up-regulation in endothelial shear responsiveness, which was further validated and localized in vascular endothelial cells, smooth muscle cells and other cells by double immunofluorescence staining. Western blotting assay demonstrated up-regulation of MMP1 and PDE2A expression dependent on the WSS. CONCLUSIONS: MMP1 and PDE2A up-regulations rely on increased WSS in development and risk of CAS, suggesting that their elevation may be potential target for diagnosis and treatment (Fig. 3, Ref. 28).