Tang Yaohan, Zhu Yaoxi, Lu Yang, Yang Hongmin, Yang Han, Li Lixia, Liu Changhu, Du Yimei, Yuan Jing
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Cardiovasc Med. 2022 Apr 7;9:741920. doi: 10.3389/fcvm.2022.741920. eCollection 2022.
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 ( = -0.84, = 0.009) and left ventricular end-diastolic diameter (LVEDd; = -0.82, = 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.
扩张型心肌病（DCM）的发展伴随着一系列代谢紊乱，导致心肌重塑或加重，但其机制仍不完全清楚。本研究旨在找出参与DCM发病的关键代谢相关基因，为该病的发病机制提供新的见解。从基因表达综合数据库下载了与DCM患者心脏相关的GSE57338、GSE116250和GSE5406数据集。对GSE57338进行分析以筛选出代谢相关的差异表达基因（DEG），而利用GSE116250和GSE5406通过R软件验证最佳基因。使用支持向量机递归特征消除算法和最小绝对收缩和选择算子算法来确定关键基因。最后，从39个代谢相关的DEG中筛选出6个并确定为最佳基因。对取自人类心脏左心室的样本进行定量逆转录聚合酶链反应（qRT-PCR）验证后发现，与非衰竭供体相比，DCM患者中只有类似α-酮戊二酸脱氢酶（OGDHL）的表达增加，而磷脂酶A2（PLA2G2）的表达显著降低。此外，在DCM心脏中还发现了除PLA2G2变化外更高的OGDHL蛋白表达，其mRNA表达与心肌Masson评分（r = -0.84，P = 0.009）和左心室舒张末期内径（LVEDd；r = -0.82，P = 0.014）呈负相关，通过进一步的生物信息学预测和qRT-PCR验证，这可能受miR-3925-5p调控。数据表明，代谢相关基因OGDHL与DCM的心肌纤维化有关，可能是DCM患者心肌重塑的生物标志物。
