Gene Expression Changes of Humans with Primary Mitral Regurgitation and Reduced Left Ventricular Ejection Fraction

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 mitra...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-03, Vol.22 (7), p.3454
Main Authors: Tsai, Feng-Chun, Chen, Yu-Lin, Yen, Kun-Chi, Chiu, Cheng-Hsun, Chen, Jui-Hsuan, Yeh, Yung-Hsin, Tsai, Pei-Chien
Format: Article
Language:English
Subjects:
Cardiomyocytes
Circadian rhythm
Collagen
Congestive heart failure
Connective tissue growth factor
Ejection fraction
Extracellular matrix
Fibrosis
Gene expression
Genes
Heart failure
Heart valves
Insulin-like growth factor-binding protein 2
Insulin-like growth factors
Microtubule-associated protein 1
Mitral valve
Proteins
Regression analysis
Regurgitation
Therapeutic applications
Transcriptomes
Ventricle
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Summary: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 decompensated MR groups. Tissue biopsies were obtained from the patients' left ventricular (LV) lateral 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 regression models, we identified 12 significant DEGs ( , , , , , , , , , , , and ). The most significant gene was (adjusted R = 0.74, = 1.80 × 10 ). We found that the majority of genes expressed in the more advanced decompensated MR group were pro-fibrotic genes associated with cardiac fibrosis. In particular, six pro-fibrotic genes ( , , , , , and ) were overexpressed and enriched in pathways involved in ECM (extracellular matrix) protein remodeling. Therapeutic interventions that antagonize these six genes may slow the progression toward decompensated MR.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22073454