Captopril Attenuates the Upregulated Connexin 43 Expression in Artery Calcification

Abstract

Objective: Vascular calcification is commonly observed in atherosclerosis and diabetes. The renin-angiotensin II system is associated with the regulation of arterial stiffening. The aim of this study was to examine whether the angiotensin-converting enzyme inhibitors captopril attenuates artery calcification.

Methods: The rat model of arterial calcification was established by a combination of warfarin and vitamin K1. Two weeks after the induction of arterial calcification, captopril treatment was initiated. One week after captopril treatment, aortic arteries were examined to determine the calcification morphology and the connexin 43 expression. Matrix Gla protein (MGP), receptor activator of nuclear factor-κB ligand (RANKL) and extracellular regulated protein kinase (ERK) pathways were examined.

Results: The morphology of the calcified arteries was significantly attenuated after captopril treatment. Consistently, captopril inhibited the increased connexin 43 expression and enhanced the decreased MGP expression in calcification arteries. Furthermore, captopril enhanced the decreased SM22 expression in calcified arteries by fluorescence assay. Finally, the calcification arteries increased the p38, p-ERK and RANKL expression, which were downregulated by captopril treatment.

Conclusions: We concluded that captopril attenuated the increased connexin 43 expression and enhanced the MGP and SM22 expression levels, which are associated with the inactivation of p-ERK, p38 and RANKL pathways in rat aortic arteries.

Keywords: Artery calcification; Captopril; Connexin 43; Matrix Gla protein; p-ERK.