Liu Lianyong, Zhou Xinglu, Chen Juan, Li Xiangqi
Department of Endocrinology and Metabolism, Punan Hospital, Shanghai, China.
Department of Endocrinology and Metabolism, Gongli Hospital, Naval Medical University, Shanghai, China.
Front Cardiovasc Med. 2022 Jul 22;9:921778. doi: 10.3389/fcvm.2022.921778. eCollection 2022.
Metabolic syndrome-associated cardiovascular disease (MetS-CVD) is a cluster of metabolism-immunity highly integrated diseases. Emerging evidence hints that mitochondrial energy metabolism may be involved in MetS-CVD development. The physiopathological role of ATP5MG, a subunit of the F0 ATPase complex, has not been fully elucidated.
In this study, we selected ATP5MG to identify the immunity-mediated pathway and mine drugs targeting this pathway for treating MetS-CVD. Using big data from public databases, we dissected co-expressed RNA (coRNA), competing endogenous RNA (ceRNA), and interacting RNA (interRNA) genes for ATP5MG.
It was identified that ATP5MG may form ceRNA with COX5A through hsa-miR-142-5p and interplay with NDUFB8, SOD1, and MDH2 through RNA-RNA interaction under the immune pathway. We dug out 251 chemicals that may target this network and identified some of them as clinical drugs. We proposed five medicines for treating MetS-CVD. Interestingly, six drugs are being tested to treat COVID-19, which unexpectedly offers a new potential host-targeting antiviral strategy.
Collectively, we revealed the potential significance of the ATP5MG-centered network for developing drugs to treat MetS-CVD, which offers insights into the epigenetic regulation for metabolism-immunity highly integrated diseases.
代谢综合征相关心血管疾病（MetS-CVD）是一组代谢与免疫高度整合的疾病。新出现的证据表明，线粒体能量代谢可能参与了MetS-CVD的发展。F0 ATP酶复合体的一个亚基ATP5MG的生理病理作用尚未完全阐明。
在本研究中，我们选择ATP5MG来确定免疫介导的途径，并挖掘针对该途径治疗MetS-CVD的药物。利用公共数据库中的大数据，我们剖析了ATP5MG的共表达RNA（coRNA）、竞争性内源RNA（ceRNA）和相互作用RNA（interRNA）基因。
研究发现，ATP5MG可能通过hsa-miR-142-5p与COX5A形成ceRNA，并在免疫途径下通过RNA-RNA相互作用与NDUFB8、SOD1和MDH2相互作用。我们挖掘出251种可能靶向该网络的化学物质，并确定其中一些为临床药物。我们提出了五种治疗MetS-CVD的药物。有趣的是，有六种药物正在进行治疗COVID-19的试验，这意外地提供了一种新的潜在宿主靶向抗病毒策略。
总体而言，我们揭示了以ATP5MG为中心的网络在开发治疗MetS-CVD药物方面的潜在意义，这为代谢与免疫高度整合疾病的表观遗传调控提供了见解。
