Related Experiment Video
Updated: May 12, 2025
Scanning Electron Microscopy of Macerated Tissue to Visualize the Extracellular Matrix
Published on: June 14, 2016
Proteome Alterations in Cardiac Fibroblasts: Insights from Experimental Myocardial Infarction and Clinical Ischaemic
Adam Russell-Hallinan1, Claire Tonry1, Lauren Kerrigan1
1Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast BT9 7BL, Northern Ireland, UK.
Insights
Cardiac fibroblasts in mice with heart attacks show significant protein changes, becoming more sensitive to fibrosis. These alterations in extracellular matrix proteins may drive cardiac remodelling and dysfunction in ischaemic heart disease.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Fibrosis Research
Background:
- Ischaemic heart disease (IHD) leads to pathological cardiac remodelling and heart failure (HF).
- Understanding alterations in cardiac fibroblasts post-myocardial infarction (MI) is crucial for IHD progression.
- Fibroblasts play a key role in the extracellular matrix (ECM) remodeling process.
Purpose of the Study:
- To investigate the proteomic changes in cardiac fibroblasts following experimental myocardial infarction (MI).
- To determine the effect of transforming growth factor-beta (TGF-β) on cardiac fibroblasts from MI mice.
- To validate findings in human tissue from patients with ischaemic cardiomyopathy (ISCM).
Main Methods:
- Experimental myocardial infarction (MI) induced in female C57BL6 mice.
- Isolation and in vitro treatment of cardiac fibroblasts with TGF-β.
- High-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) proteomic analysis.
- Validation using mass spectrometry data from human left ventricular tissues (ISCM vs. non-failing NF).
Main Results:
- Significant protein expression changes in mouse cardiac fibroblasts were observed 1 month post-MI.
- TGF-β treatment significantly altered fibroblasts from MI mice, indicating heightened sensitivity.
- Altered extracellular matrix (ECM) proteins in MI fibroblasts treated with TGF-β were associated with cardiac remodelling.
- Lysyl oxidase (Lox) protein levels were significantly changed in both mouse MI fibroblasts and human ISCM tissues.
Conclusions:
- Cardiac fibroblasts isolated from MI mice exhibit increased susceptibility to pathogenic traits upon TGF-β stimulation.
- Specific ECM proteins are altered, potentially contributing to MI-associated cardiac dysfunction.
- These findings highlight the role of fibroblast activation and ECM remodeling in IHD progression.
Abstract:
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.
Related Concept Videos
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:17Pathophysiology of Heart Failure