iTRAQ analysis of a mouse acute myocardial infarction model reveals that vitamin D binding protein promotes cardiomyocyte apoptosis after hypoxia

Abstract

The proteome profile changes after acute myocardial infarction (AMI) and the roles played by important protein species remain poorly understood. Here, we constructed a mouse AMI model by ligating the left coronary artery of male C57B/6J mice to investigate the molecular changes after AMI on the protein level. Total proteins of the left ventricle were extracted and quantitatively analyzed by isobaric tags using relative and absolute quantitation (iTRAQ) technologies. The transcript and protein levels of important genes were further validated using quantitative polymerase chain reaction and western blot. An oxygen and glucose deprivation/reperfusion cell model was constructed using H9C2 cells to further validate the expression patterns and functions of important proteins after hypoxia. Seven hundred seventy-six proteins were identified as differentially abundant proteins after AMI, of which 406 were accumulated, and 370 were reduced. Gene ontology enrichment analysis showed that the most enriched molecular function category terms were binding, including calcium ion biding, GTP binding, actin binding and lipid binding. The expression levels of vitamin D binding protein (VDBP) and its related proteins were increased in both left ventricular tissue and H9C2 cells after ischemia-hypoxia. Overexpression of VDBP in H9C2 cells reduced vitamin D receptor and promoted the cell apoptosis rate after hypoxia. Our data provided new insights into proteome profile changes after AMI and indicated that VDBP could promote cardiomyocyte apoptosis after hypoxia.

Nontraditional Cardiovascular Biomarkers and Risk Factors: Rationale and Future Perspectives

“…Nonetheless, in serum samples of patients with ST-elevation myocardial infarction (STEMI) the proteomic approach identified increased levels of DBP when compared to control donors, confirmed by the Western blot analysis [ 36 ]. These findings were confirmed by those recently published on the proteome profile changes after acute myocardial infarction (AMI) in an experimental model, where the expression levels of DBP and vitamin D receptor (VDR) were found increased in both left ventricular tissue of AMI mouse model, suggesting that DBP might be involved in left ventricular remodeling, and H9C2 cells, promoting cardiomyocyte apoptosis, after hypoxia [ 37 ].…”

Proteomic and metabolomic characterization of cardiac tissue in acute myocardial ischemia injury rats

“…Integrated proteomic-metabolomics is a powerful combination [8] and provides a better understanding of dynamic molecular change. Some studies have reported the changes of metabolites and proteins in plasma or myocardium after MI [9][10][11]; however, the integrated proteomic-metabolomics in myocardium after an MI has not been reported. Thus, we designed an integrated proteomic-metabolomics study, to comprehensively understand the pathological changes and the mechanisms of MI.…”

The Identification and Validation of Hub Genes Associated with Acute Myocardial Infarction Using Weighted Gene Co-Expression Network Analysis

“…According to the GO analysis, the BP term 'translation' mainly affected protein synthesis, which otherwise resulted in the production of dysfunctional proteins. 'Translation' has been previously reported correlated to AMI [25]. Donko et al also stated that the unique genes in degenerative heart disease encoded proteins in the 80 S ribosome complex (term 'translation') [26].…”