PDGF-AB Reduces Myofibroblast Differentiation Without Increasing Proliferation After Myocardial Infarction

Hume, Robert D. and Deshmukh, Tejas and Doan, Tram and Shim, Woo Jun and Kanagalingam, Shaan and Tallapragada, Vikram and Rashid, Fairooj and Marcuello, Maria and Blessing, Daniel and Selvakumar, Dinesh and Raguram, Kalyan and Pathan, Faraz and Graham, Dinny and Ounzain, Samir and Kizana, Eddy and Harvey, Richard P. and Palpant, Nathan J. and Chong, James J.H. (2023) PDGF-AB Reduces Myofibroblast Differentiation Without Increasing Proliferation After Myocardial Infarction. JACC: Basic to Translational Science, 8 (6). pp.658-674. ISSN 2452302X

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Link to published document: http://doi.org/10.1016/j.jacbts.2022.11.006


After myocardial infarction (MI), fibroblasts progress from proliferative to myofibroblast states, resulting in fibrosis. Platelet-derived growth factors (PDGFs) are reported to induce fibroblast proliferation, myofibroblast differentiation, and fibrosis. However, we have previously shown that PDGFs improve heart function post-MI without increasing fibrosis. We treated human cardiac fibroblasts with PDGF isoforms then performed RNA sequencing to show that PDGFs reduced cardiac fibroblasts myofibroblast differentiation and downregulated cell cycle pathways. Using mouse/pig MI models, we reveal that PDGF-AB infusion increases cell-cell interactions, reduces myofibroblast differentiation, does not affect proliferation, and accelerates scar formation. RNA sequencing of pig hearts after MI showed that PDGF-AB reduces inflammatory cytokines and alters both transcript variants and long noncoding RNA expression in cell cycle pathways. We propose that PDGF-AB could be used therapeutically to manipulate post-MI scar maturation with subsequent beneficial effects on cardiac function.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 02 Apr 2024 02:29
Last Modified: 02 Apr 2024 02:29
URI: http://eprints.victorchang.edu.au/id/eprint/1434

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