Experimental myocardial infarction and subsequent TGF-β treatment significantly altered extracellular matrix protein expression, notably Lox, in both mouse cardiac fibroblasts and human ischaemic tissue.
Cardiac fibroblasts from post-MI hearts exhibit heightened sensitivity to pro-fibrotic factors like TGF-β, leading to significant alterations in ECM proteins such as Lox that may drive pathological cardiac remodeling.
Ischaemic heart disease (IHD) is a chronic condition that can cause pathological cardiac remodelling and heart failure (HF). In this study, we sought to determine how cardiac fibroblasts were altered post-experimental myocardial infarction (MI). Female C57BL6 mice underwent experimental MI by permanent left coronary artery ligation. Cardiac fibroblasts were isolated from extracted heart tissue of experimental MI mice and subsequently treated with the pro-fibrotic cytokine, TGF-β, for 24 h and analysed using high throughput LC-MS/MS analysis. Findings were validated using mass spectrometry data generated from human left ventricular tissue analysis, which were collected from patients with ischaemic cardiomyopathy (ISCM) and age/sex-matched patients without clinical HF (NF). Proteomic analysis revealed significant protein expression changes in mouse cardiac fibroblasts after MI. These changes were most pronounced at 1 month post-MI, compared to earlier time points (3 days and 1 week). TGF-β treatment profoundly affected fibroblast cells extracted from MI mice, indicating a heightened sensitivity to pro-fibrotic factors after myocardial injury. Extracellular matrix (ECM) proteins significantly altered in MI fibroblasts following TGF-β treatment were significantly associated with cardiac remodelling. Notably, Lox was significantly changed in both isolated fibroblasts treated with TGF-β from experiment MI mice and human ISCM. Isolated cardiac fibroblasts from MI mice are more susceptible to developing pathogenic traits following TGF-β treatment than isolated fibroblasts from normal heart tissue. ECM proteins associated with these enhanced fibroblast activities and functions are evident. These altered proteins may play a functional role in MI-associated cardiac dysfunction.
Russell‐Hallinan et al. (Fri,) conducted a other in Ischaemic cardiomyopathy and myocardial infarction. Experimental myocardial infarction and TGF-β treatment vs. Normal heart tissue and patients without clinical heart failure was evaluated on Proteome alterations and protein expression changes in cardiac fibroblasts. Experimental myocardial infarction and subsequent TGF-β treatment significantly altered extracellular matrix protein expression, notably Lox, in both mouse cardiac fibroblasts and human ischaemic tissue.