miR-21-5p promotes osteogenic differentiation and calcification of valvular interstitial cells by targeting TGFBI in calcific aortic valve disease

Abstract

Abstract Calcific aortic valve disease (CAVD) is the most common heart relating disease with high morbidity and mortality, especially in elderly population. A previous recent multi-omics study suggested a novel CAVD molecular interaction network contained miR-21-5p. To confirm the association between miR-21-5p and CAVD progression, in this study, we investigated the roles of miR-21-5p in the mineralization process of aortic valves obtained from CAVD patients and paired normal tissues. Valvular intersitial cells (VICs) were isolated from clinic samples and maintained for the following assays. RT-qPCR was utilized for detection of miR-21-5p and related protein expression levels to confirm the related factors in CAVD progression. Western blotting was applied to strengthen the results of RT-qPCR and confirm osterogenic differentiation of VICs via biomarker detection. The staining of alkaline phosphatase (ALP) and alizarin red was performed to assess the degree of VIC mineralization. We found that miR-21-5p was remarkably increased in calcified aortic valves (AVs) whereas TGFBI was diminished in CAVD samples compared to the paired normal tissues from CAVD patients. Additionally, TGFBI was targeted by miR-21-5p. Furthermore, overexpressing TGFBI could block VIC osteogenic differetiation mediated by miR-21-5p. To sum up, miR-21-5p promotes VIC osteogenic differentiation and calcificaion via TGFBI in CAVD progression. Our work might bring a sight on underlying mechansims of CAVD progression and provide a possible therapeutic target for diagnosis and treatment.