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. Since calcified aortic valves (AVs) have distinct miRNA and gene expression profiles compared to healthy AVs, microRNA (miRNA) and messenger RNA (mRNA) based therapies hold a lot of promise as potential drugs. In this regard, mechanosensitivity of AV calcification-specific miRNAs and mRNAs can serve as a critical criterion in identifying the most effective candidates, as it has been shown that altered mechanical environment plays a key role in AV pathogenesis. To this day, majority of the studies have focused on disturbed flow-induced changes in miRNA and mRNA expression related to CAVD. However, identification and functional description of stretch-sensitive miRNAs and mRNAs in CAVD are poorly studied. Hence, this work aims to identify and functionally describe AV calcification-specific miRNAs and mRNAs that are stretch-sensitive. Our hypothesis is that stretch-sensitive miRNAs and mRNAs play a significant role in the pathogenesis of AV calcification; consequently, overexpression or inhibition of these miRNAs and mRNAs are potential candidates for therapeutic application. To test this hypothesis, the following aims are proposed: (1) investigate the effects of physiological and pathological cyclic stretch on miRNA expression in AV, and (2) investigate the effects of physiological and pathological cyclic stretch on mRNA expression in AV. This research work will help in identifying important stretch-sensitive miRNAs and mRNAs as potential therapeutic candidates for CAVD.Ph.D
