MicroRNA‐638 inhibits human aortic valve interstitial cell calcification by targeting Sp7

Abstract

Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR‐638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT‐PCR results demonstrating miR‐638 was obviously up‐regulated in calcific aortic valves compared with non‐calcific valves. We also proved that miR‐638 was significantly up‐regulated during hAVICs osteogenic differentiation. Overexpression of miR‐638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down‐regulation of miR‐638 enhance the process. Target prediction analysis and dual‐luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR‐638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up‐regulation miR‐638. Our data indicated that miR‐638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR‐638 may be a potential therapeutic target for CAVD.

Recent Advances of Osterix Transcription Factor in Osteoblast Differentiation and Bone Formation

“…It has been proved that miR-27a and miR-96 etc. regulate osteogenesis by targeting Osx (As shown in Figure 4 ) ( Zhang et al, 2011 ; Shi et al, 2013 ; Zhang et al, 2018 ; Jiao et al, 2019 ). They suppress osteogenic differentiation by decreasing Osx expression directly.…”

M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy

“…Osteogenic reprogramming of AVICs has been reported to be closely related to the pathological process of CAVD ( Jiao et al, 2019 ). Abnormal M1 polarization of macrophages partially explained osteogenic calcification of AVICs in CAVD ( Lu et al, 2022 ).…”

Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis

“…Wong et al showed miR-638 distinguished heart failure with reduced vs. preserved left ventricular ejection fraction and offers better diagnosis than N-terminal pro-brain natriuretic peptide [ 119 ]. Jiao et al indicated that miR-638 is upregulated in human calcific aortic valves (hAVICs) compared with non-calcific valves and was significantly upregulated during hAVICs osteogenic differentiation [ 120 ]. This constitutes a promising noninvasive diagnostic as well as prognostic biomarker in cardiovascular pathologies risk.…”