The Potential of Metabolism-Related Gene OGDHL as a Biomarker for Myocardial Remodeling in Dilated Cardiomyopathy

Abstract

The development of dilated cardiomyopathy (DCM) is accompanied by a series of metabolic disorders, resulting in myocardial remodeling or exacerbation, while the mechanism remains not completely clear. This study was to find out the key metabolism-related genes involved in the onset of DCM, providing new insight into the pathogenesis of this disease. The datasets of GSE57338, GSE116250, and GSE5406 associated with hearts of patients with DCM were downloaded from the Gene Expression Omnibus database. GSE57338 was analyzed to screen out metabolism-related differentially expressed genes (DEGs), while GSE116250 and GSE5406 were utilized to verify the optimal genes through R software. Support vector machine recursive feature elimination algorithm and least absolute shrinkage and selection operator algorithm were used to determine key genes. Finally, 6 of 39 metabolism-related DEGs were screened out and identified as the optimal genes. After quantitative reverse-transcription polymerase chain reaction (qRT-PCR) validation performed on the samples drawn from the left ventricles of human hearts, it showed that only the expression of oxoglutarate dehydrogenase-like (OGDHL) increased while PLA2G2 decreased significantly in patients with DCM compared with non-failing donors, respectively. Furthermore, the higher OGDHL protein expression, except the change of PLA2G2, was also found in DCM hearts, and its mRNA expression was negatively correlated with myocardial Masson’s scores (r = –0.84, P = 0.009) and left ventricular end-diastolic diameter (LVEDd; r = –0.82, P = 0.014), which might be regulated by miR-3925-5p through further bioinformatics prediction and qRT-PCR verification. The data then suggested that the metabolism-related gene OGDHL was associated with myocardial fibrosis of DCM and probably a biomarker for myocardial remodeling in patients with DCM.