Aberrant Epicardial Adipose Tissue Extracellular Matrix Remodeling in Patients with Severe Ischemic Cardiomyopathy: Insight from Comparative Quantitative Proteomics

Abstract

There is ample evidence indicating that epicardial adipose tissue (EAT) volume and thickness is positively associated with coronary artery disease (CAD). However, the exact pathological changes in the human EAT after myocardial ischemia remains largely unclear. In the current study, we applied a comparative quantitative proteomics to elucidate the altered biological processes in the EAT of ischemic cardiomyopathy (ICM) patients. A total of 1649 proteins were successfully quantified in our study, among which 165 proteins were significantly changed (ratio <0.8 or >1.2 fold and p < 0.05 in both repetitions) in EAT of ICM individuals. Gene ontology (GO) enrichment analysis revealed that cardiac structure and cellular metabolism were over-represented among these regulated proteins. The hypertrophic cardiomyopathy, adrenergic signaling in cardiomyocytes, extracellular matrix (ECM)-receptor interaction, phagosome, Glycolysis/Gluconeogenesis, and PPAR signaling pathway were highlighted by the KEGG PATHWAY analysis. More importantly, we found that the proteins responsible for extracellular matrix organization were dramatically increased in EAT of ICM patients. In addition, the picrosirius red (PSR) staining results showed that the collagen fiber content was prominently increased, which indicated the EAT of ICM individuals underwent extracellular matrix remodeling and ERK1/2 activation maybe responsible for these pathological changes partially.

Epicardial adipose tissue: at the heart of the obesity complications

“…In fact, in line with other fat depots [56,57], not only extracellular matrix proteins are remarkably increased in EAT in cardiac pathological conditions [58], but EAT may also induce fibrosis in the neighboring myocardium through the secretion of profibrotic mediators including inflammatory cytokines, growth factors and matrix metalloproteinases [59,60] (Fig. 1).…”

Impact of left ventricular assist device therapy on the cardiac proteome and metabolome composition in ischemic cardiomyopathy

“…In our study, we also observe differential regulation of some metabolic enzymes or components of the respiratory chain; however, the impact is too diffuse to be observed as in GO‐ enrichment analysis. Similarly, Jiang et al report an impact of ICM on metabolic enzymes, albeit without direct comparison to DCM . Ortega et al showed endoplasmic reticulum biology is differentially affected between ICM and DCM; our global approach lacks the methodological focus to investigate this aspect.…”

“…Similarly, Jiang et al report an impact of ICM on metabolic enzymes, albeit without direct comparison to DCM. 32 Ortega et al showed endoplasmic reticulum biology is differentially affected between ICM and DCM 33 ; our global approach lacks the methodological focus to investigate this aspect.…”

Quantitative proteomics reveal the alterations in the spinal�cord after myocardial ischemia‑reperfusion injury in rats

“…were performed on a TripleTOF 5600+ System coupled with an Ultra 1D Plus nano-liquid chromatography device (SCIEX) as previous reported (45). Dried peptides were dissolved in 0.1% formic acid, 2% acetonitrile and 98% H 2 O.…”

“…A total of 90 proteins are differentially expressed in the spinal cord after IR injury. To identify the differentially expressed proteins in the spinal cord that are regulated by myocardial injury, a filtering rule was set as previously reported (41,45), to screen those differentially expressed proteins: Proteins with 50% change of ratio in each replicate, or P<0.05 in each replicate and additionally 50% change of average ratio, were considered to be differentially expressed. Among the whole quantitative dataset, 33 spinal cord proteins were found to be upregulated in IR rats, whereas 57 proteins were downregulated ( Fig.…”