Gene expression changes of humans with primary mitral regurgitation and reduced left ventricular ejection fraction

Feng Chun Tsai, Yu Lin Chen, Kun Chi Yen, Cheng Hsun Chiu, Jui Hsuan Chen, Yung Hsin Yeh, Pei Chien Tsai*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

6 引文 斯高帕斯(Scopus)

摘要

Patients with primary mitral regurgitation (MR) may remain asymptomatic for many years. For unknown reasons, some shift from a compensated to a decompensated state and progress to fatal heart failure. To elucidate the genetic determinants of this process, we recruited 28 patients who underwent mitral valve surgery and stratified them into control, compensated MR, and de-compensated MR groups. Tissue biopsies were obtained from the patients’ left ventricular (LV) lat-eral wall for a transcriptome‐wide profiling of 64,769 probes to identify differentially expressed genes (DEGs). Using cutoff values at the 1% FDR significance level and sex‐ and age‐adjusted re-gression models, we identified 12 significant DEGs (CTGF, MAP1B, SERPINE1, MYH9, MICAL2, MYO1D, CRY1, AQP7P3, HTRA1, PRSS23, IGFBP2, and FN1). The most significant gene was CTGF (adjusted R2 = 0.74, p = 1.80 × 10−8). We found that the majority of genes expressed in the more advanced decompensated MR group were pro‐fibrotic genes associated with cardiac fibrosis. In par-ticular, six pro‐fibrotic genes (CTGF, SERPINE1, MYH9, HTRA1, PRSS23, and FN1) were overex-pressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompen-sated MR.

原文英語
文章編號3454
期刊International Journal of Molecular Sciences
22
發行號7
DOIs
出版狀態已出版 - 01 04 2021

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© 2021 by the author. Licensee MDPI, Basel, Switzerland.

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