Jiang Zhaochang, Lu Haohao, Gao Beibei, Huang Jinyu, Ding Yu
Department of Pathology, Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China.
Zhejiang Center of Laboratory Animals, Hangzhou Medical College, Hangzhou, Zhejiang, 310063, People's Republic of China.
J Inflamm Res. 2024 Sep 23;17:6645-6659. doi: 10.2147/JIR.S469297. eCollection 2024.
Coronary microembolization (CME) can result in cardiac dysfunction, severe arrhythmias, and a reduced coronary flow reserve. Impairment of mitochondrial energy metabolism has been implicated in the progression and pathogenesis of CME; however, its role remains largely undetermined. This study aimed to explore alterations in mitochondria-related genes in CME.
A rat model of CME was successfully established by injecting plastic microspheres into the left ventricle. The cardiac tissues of the two groups were sequenced and mitochondrial functions were assessed.
Using RNA-Seq, together with GO and KEGG enrichment analyses, we identified 3822 differentially expressed genes (DEGs) in CME rats compared to control rats, and 101 DEGs were mitochondria-related genes. Notably, 36 DEGs were up-regulated and 65 DEGs were down-regulated (CME vs control). In particular, the oxidative phosphorylation (OXPHOS) and mitochondrial electron transport were obviously down-regulated in the CME group. Functional analysis revealed that CME mice exhibited marked reductions in ATP and mitochondrial membrane potential (MMP), by contrast, the production of reactive oxygen species (ROS) was much higher in CME mice than in controls. Protein-protein interaction (PPI) and quantitative PCR (qPCR) validation suggested that eight hub genes including Cmpk2, Isg15, Acsl1, Etfb, Ndufa8, Adhfe1, Gabarapl1 and Acot13 were down-regulated in CME, whereas Aldh18a1 and Hspa5 were up-regulated.
Our findings suggest that dysfunctions in mitochondrial activity and metabolism are important mechanisms for CME, and mitochondria-related DEGs may be potential therapeutic targets for CME.
冠状动脉微栓塞（CME）可导致心脏功能障碍、严重心律失常和冠状动脉血流储备降低。线粒体能量代谢受损与CME的进展和发病机制有关；然而，其作用在很大程度上仍未确定。本研究旨在探讨CME中线粒体相关基因的变化。
通过向左心室注射塑料微球成功建立CME大鼠模型。对两组心脏组织进行测序并评估线粒体功能。
通过RNA测序以及GO和KEGG富集分析，我们在CME大鼠与对照大鼠中鉴定出3822个差异表达基因（DEG），其中101个DEG是线粒体相关基因。值得注意的是，36个DEG上调，65个DEG下调（CME组与对照组相比）。特别是，CME组中氧化磷酸化（OXPHOS）和线粒体电子传递明显下调。功能分析显示，CME小鼠的ATP和线粒体膜电位（MMP）显著降低，相比之下，CME小鼠中活性氧（ROS）的产生比对照组高得多。蛋白质-蛋白质相互作用（PPI）和定量PCR（qPCR）验证表明，包括Cmpk2、Isg15、Acsl1、Etfb、Ndufa8、Adhfe1、Gabarapl1和Acot13在内的8个枢纽基因在CME中下调，而Aldh18a1和Hspa5上调。
我们的研究结果表明，线粒体活性和代谢功能障碍是CME的重要机制，线粒体相关DEG可能是CME的潜在治疗靶点。
