Zhang Fan, Cheng Naixuan, Han Yingchun, Zhang Congcong, Zhang Haibo
Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Vascular Diseases, Beijing, China.
Front Genet. 2021 Oct 22;12:722564. doi: 10.3389/fgene.2021.722564. eCollection 2021.
Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene and . In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs the Wnt/β-Catenin pathway, which may further provide a new therapeutic target for CAVD.
钙化性主动脉瓣疾病（CAVD）是最常见的结构性心脏病，其发病率随老年人口增加而上升。已确定几种微小RNA（miRNA）在CAVD中起关键作用，仍有许多miRNA有待探索。在本研究中，通过miRNA测序对CAVD中的miRNA表达特征进行了无偏分析，我们发现，与正常对照瓣膜相比，钙化主动脉瓣中有152种miRNA上调，186种miRNA下调。这些差异表达的miRNA的功能与细胞分化、凋亡、黏附和免疫反应过程相关。在下调的miRNA中，miR-139-5p的表达水平与成骨基因呈负相关，并且在原代人主动脉瓣间质细胞（VICs）的成骨分化过程中miR-139-5p也下调。随后的功能研究表明，miR-139-5p过表达通过负向调节促成骨基因和的表达来抑制VICs的成骨分化。总之，这些结果表明miR-139-5p在VICs通过Wnt/β-连环蛋白途径的成骨分化中起重要作用，这可能进一步为CAVD提供新的治疗靶点。
