Role of microRNA 214 in cyclic stretch induced aortic valve pathogenesis

Abstract

Calcific aortic valve disease (CAVD) is one of the most prevalent valvular diseases among the elderly population. Unfortunately, there are no therapeutic drugs available to treat this disease. In this regard, mechanosensitive miRNAs have been considered as potential therapeutic candidates for CAVD, due to their role in modulating gene expression. microRNA 214 (miR-214) is a major miRNA which is significantly downregulated in calcified aortic valves (AVs). Previously, miR-214 has been shown to be shear-sensitive in AV. However, the effect of cyclic stretch on miR-214 expression and its functional effect in AV are poorly understood. Hence, this work aims to evaluate the effect of cyclic stretch on the expression of miR-214 and one of its well-known targets (ATF4) and downstream genes (CHOP and BCL2L1) in porcine AVs ex vivo. Also, the effect of miR-214 overexpression on porcine AV calcification is evaluated. This would give a better understanding on the potential therapeutic role of miR-214 in CAVD.