Date Published: January 31, 2019
Publisher: Impact Journals
Author(s): Chenyang Duan, Zhezhe Cao, Fuqin Tang, Zhao Jian, Chunshui Liang, Hong Liu, Yingbin Xiao, Liangming Liu, Ruiyan Ma.
Aortic valve stenosis is the most common cause of morbidity and mortality in valvular heart disease in aged people. Both microRNA (miRNA) and mRNA are potential targets for the diagnosis and therapeutic intervention of myocardial ischemia induced by calcified aortic valve stenosis (CAVS), with unclear mechanisms. Here, 3 gene expression profiles of 47 male participants were applied to generate shared differentially expressed genes (DEGs) with significant major biological functions. Moreover, 20 hub genes were generated by a Weighted Genes Co-Expression Network Analysis (WGCNA) and were cross-linked to miRNA based on miRanda/miRwalk2 databases. Integrated miRNA/mRNA analysis identified several novel miRNAs and targeted genes as diagnostic/prognostic biomarkers or therapeutic targets in CAVS patients. In addition, the clinical data suggested that myocardial hypertrophy and myocardial ischemia in CAVS patients are likely associated with hub genes and the upstream regulatory miRNAs. Together, our data provide evidence that miRNAs and their targeted genes play an important role in the pathogenesis of myocardial hypertrophy and ischemia in patients with CAVS.
Myocardial ischemia (MI) is a pathological condition in which the cardiac blood perfusion as well as oxygen supply reduce significantly. Many factors may induce myocardial ischemia, such as valve disease, changes in blood viscosity, and myocardial lesions, etc. During aging, calcified aortic valve disease (CAVD) gradually increases with enhanced myocardial hypertrophy, myocardial ischemia, and cardiac dysfunction [1,2], eventually leading to severe aortic stenosis (AS), also known as calcified aortic stenosis (CAVS) . The current effective treatment for CAVS is valve replacement but the outcome of medical trials of therapies aiming to delay or prevent the progression of myocardial ischemia induced by CAVS are not satisfactory [4,5]. The Current preconditioning and post-conditioning measures for myocardial ischemia are mainly aimed at calcium overload, increased ROS and inflammatory reactions after CAVS, which are closely associated with cardiac mitochondria functions. Therefore, we hypothesis that the prognosis of myocardial ischemia induced by CAVS may be related to altered mitochondrial function in CAVS and improvement of mitochondria functions may be useful to assess or delay the progression of myocardial ischemia after CAVS.
In this study, three gene expression profiles of aortic valve tissue in patients with and without CAVS were included. Functional enrichment analysis demonstrated that the mitochondrial function variation plays an important role in the pathogenesis of CAVS. Moreover, the integrated miRNA/mRNA analysis results uncovered several miRNAs and genes that can be used as diagnostic biomarkers or in therapeutic approaches.