Bioinformatic analysis of membrane and associated proteins in murine cardiomyocytes and human myocardium

Abstract

In the current study we examined several proteomic- and RNA-Seq-based datasets of cardiac-enriched, cell-surface and membrane-associated proteins in human fetal and mouse neonatal ventricular cardiomyocytes. By integrating available microarray and tissue expression profiles with MGI phenotypic analysis, we identified 173 membrane-associated proteins that are cardiac-enriched, conserved amongst eukaryotic species, and have not yet been linked to a ‘cardiac’ Phenotype-Ontology. To highlight the utility of this dataset, we selected several proteins to investigate more carefully, including FAM162A, MCT1, and COX20, to show cardiac enrichment, subcellular distribution and expression patterns in disease. We performed three-dimensional confocal imaging analysis to validate subcellular localization and expression in adult mouse ventricular cardiomyocytes. FAM162A, MCT1, and COX20 were expressed differentially at the transcriptomic and proteomic levels in multiple models of mouse and human heart diseases and may represent potential diagnostic and therapeutic targets for human dilated and ischemic cardiomyopathies. Altogether, we believe this comprehensive cardiomyocyte membrane proteome dataset will prove instrumental to future investigations aimed at characterizing heart disease markers and/or therapeutic targets for heart failure.

Integrated Analysis of Weighted Gene Coexpression Network Analysis Identifying Six Genes as Novel Biomarkers for Alzheimer’s Disease

“…For example, relevant studies demonstrated that FAM162A overexpression induces canonical mitochondrial cell death in multiple cells, including prostate cancer cells [ 37 ]. Furthermore, Lee et al found that multiple genes that are upregulated, including FAM162A , are cardiac enriched and may have an effect on the progression of heart failure [ 39 ]. FAM162A was identified as an upregulated gene in several diseases [ 39 , 40 ]; however, we found that this gene was downregulated in AD, and the specific mechanism involving AD remains to be further explored.…”

Cardiac Energy Metabolism in Heart Failure

“…97 In support of this decrease in glucose oxidation, myocardial biopsies from patients with heart failure were found to have reduced expression of MCT1 (monocarboxylate transporter 1), PDH, MPCs, and of pyruvate/ alanine aminotransferases, suggesting reduced transport and metabolism of pyruvate. 98,99 However, in a study in pacing-induced heart failure in dogs an increase in glucose oxidation was observed. 44 Increased anaplerosis represents an important adaptation in the failing heart mediated by increased carboxylation of pyruvate by ME1 (malic enzyme 1), which is induced in response to pressure overload and in failing human hearts.…”

Identification and validation of potential hypoxia-related genes associated with coronary artery disease

“…A previous study discovered that variants of PPFIA4 were associated with supernormal coronary arteries and atrial fibrillation ( Low et al, 2017 ; Kim et al, 2022 ). FAM162A may serve as possible therapeutic and diagnostic targets for human dilated and ischemic cardiomyopathies because it was differentially expressed at the transcriptomic and proteomic levels in a number of rodent and human heart disease models ( Lee et al, 2020 ). Recently, it was found that Trophoblast Glycoprotein (TPBG) was expressed in adventitial pericyte-like cells (APCs) in situ and after in vitro expansion and was essential for migration and proangiogenic activities ( Spencer et al, 2019 ).…”