Journal
JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 5, Pages 2867-2881Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00098
Keywords
cardiovascular disease; cardiac fibroblasts; myofibroblasts; cardiac fibrosis and remodeling; myocardial infarction; mass spectrometry
Categories
Funding
- Ted Rogers Centre for Heart Research Translational Biology and Engineering Program (TBEP)
- University of Toronto's Medicine by Design initiative
- Canada First Research Excellence Fund
- Canadian Institutes of Health Research [375597]
- Canada Foundation for Innovation (CFI) [36349, 36050, 38861, 38430]
- Ontario Research Fund (ORF)
Ask authors/readers for more resources
Heart failure is associated with pathological remodeling of the myocardium, with activated cardiac fibroblasts playing a crucial role in fibrosis and scar formation. Mass spectrometry analysis revealed global activation of cardiac fibroblasts post-injury, with differential protein expression between fibroblasts from remote and infarct regions of injured hearts. These findings suggest that myocardial infarction induces significant changes to the cardiac fibroblast proteome, with differences reflecting proximity to the site of injury.
Heart failure (HF) is associated with pathological remodeling of the myocardium, including the initiation of fibrosis and scar formation by activated cardiac fibroblasts (CFs). Although early CF-dependent scar formation helps prevent cardiac rupture by maintaining the heart's structural integrity, ongoing deposition of the extracellular matrix in the remote and infarct regions can reduce tissue compliance, impair cardiac function, and accelerate progression to HF. In our study, we conducted mass spectrometry (MS) analysis to identify differentially altered proteins and signaling pathways between CFs isolated from 7 day sham and infarcted murine hearts. Surprisingly, CFs from both the remote and infarct regions of injured hearts had a wide number of similarly altered proteins and signaling pathways that were consistent with fibrosis and activation into pathological myofibroblasts. Specifically, proteins enriched in CFs isolated from MI hearts were involved in pathways pertaining to cell-cell and cell-matrix adhesion, chaperone-mediated protein folding, and collagen fibril organization. These results, together with principal component analyses, provided evidence of global CF activation postinjury. Interestingly, however, direct comparisons between CFs from the remote and infarct regions of injured hearts identified 15 differentially expressed proteins between MI remote and MI infarct CFs. Eleven of these proteins (Gpc1, Cthrc1, Vmac, Nexn, Znf185, Sprr1a, Specc1, Emb, Limd2, Pawr, and Mcam) were higher in MI infarct CFs, whereas four proteins (Gstt1, Gstm1, Tceal3, and Inmt) were higher in MI remote CFs. Collectively, our study shows that MI injury induced global changes to the CF proteome, with the magnitude of change reflecting their relative proximity to the site of injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available