Extensive Mitochondrial Proteome Disturbance Lie in the Early Stage of Acute Myocardial Ischemia

ABSTRACT: Background： Mitochondria malfunction leads to myocardial energy metabolism remodeling during myocardial ischemia. However, the mitochondrial proteome profile during this period has not been clarified. Methods：Acute myocardial ischemia (MI) model was established by high ligation of left anterior descending (LAD) coronary artery in 8-week-old C57BL/6N mice. After 15 min of ligation, the animals were sacrificed and hearts were collected. Myocardium ultrastructure was observed by transmission electron microscope (TEM). The cardiac mitochondrial proteome profile was analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach and bioinformatics analysis. Results：Observation of TEM showed the mitochondria outer membrane was dissolved, inner membrane (cristae) was corrupted and disappeared extensively in the MI group. The MMP was decreased in the MI group compared with the Sham (p < 0.05). More than 1,700 mitochondrial proteins were screened by LC-MS/MS analysis, and 119 differentially expressed proteins were identified in the MI group (p < 0.05). 27 of the differential proteins were up-regulated and 16 were down-regulated, and the other 76 proteins showed differences between “with or without”. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis showed that endopeptidase activity regulation, mitochondrial inner membrane, oxidative phosphorylation, hypoxia-inducible factor-1 (HIF-1) signal pathway, pentose phosphate pathway, and PPAR signal pathway were involved in the pathophysiological process in the early stage of acute myocardial ischemia. Conclusion：Extensive and significant changes of mitochondrial proteins along with mitochondria microstructure damages arise in the early stage of acute MI. Series of the proteins are crucial in the pathways of mitochondrial dysfunction, positive regulation of mitochondrion autophagy in respiratory, collagen-containing extracellular matrix, and metabolism. Further studies are needed to clarify the roles and details of these proteins in acute MI injury.

ORGANISM(S): Mus Musculus

SUBMITTER: Jun he  

PROVIDER: PXD026207 | iProX | Fri May 21 00:00:00 BST 2021

REPOSITORIES: iProX