Identifying Potential Mitochondrial Proteome Signatures Associated with the Pathogenesis of Pulmonary Arterial Hypertension in the Rat Model.

Pulmonary arterial hypertension (PAH) is a severe and progressive disease that affects the heart and lungs and a global health concern that impacts individuals and society. Studies have reported that some proteins related to mitochondrial metabolic functions could play an essential role in the pathogenesis of PAH, and their specific expression and biological function are still unclear. We successfully constructed a monocrotaline- (MCT-) induced PAH rat model in the present research. Then, the label-free quantification proteomic technique was used to determine mitochondrial proteins between the PAH group (n = 6) and the normal group (n = 6). Besides, we identified 1346 mitochondrial differentially expressed proteins (DEPs) between these two groups. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the mainly mitochondrial DEPs' biological functions and the signal pathways. Based on the protein-protein interaction (PPI) network construction and functional enrichment, we screened 19 upregulated mitochondrial genes (Psmd1, Psmc4, Psmd13, Psmc2, etc.) and 123 downregulated mitochondrial genes (Uqcrfs1, Uqcrc1, Atp5c1, Atp5a1, Uqcrc2, etc.) in rats with PAH. Furthermore, in an independent cohort dataset and experiments with rat lung tissue using qPCR, validation results consistently showed that 6 upregulated mitochondrial genes (Psmd2, Psmc4, Psmc3, Psmc5, Psmd13, and Psmc2) and 3 downregulated mitochondrial genes (Lipe, Cat, and Prkce) were significantly differentially expressed in the lung tissue of PAH rats. Using the RNAInter database, we predict potential miRNA target hub mitochondrial genes at the transcriptome level. We also identified bortezomib and carfilzomib as the potential drugs for treatment in PAH. Finally, this study provides us with a new perspective on critical biomarkers and treatment strategies in PAH.

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

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.