The novel cardiokine GDF3 predicts adverse fibrotic remodeling post-myocardial infarction
Abstract Background Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery.Objective To explore the regulation of fibroblasts proliferation through a paracrine action of cardiac stromal cells post-MIMethods We carried out a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of secreted proteins candidates were subsequently analyzed in mouse and human hearts and plasmas. The relation between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-elevation MI and serial cardiac magnetic resonance imaging (MRI) evaluations.Results Cardiac stromal PW1+ cells undergo a change in paracrine behavior post-MI and secrete factors that promote fibroblast proliferation. Among these factors, growth differentiation factor 3 (GDF3), a member of the transforming growth factor-β family, was markedly upregulated in the ischemic hearts and induced fibroblast proliferation at high level. In humans, GDF3 was detected in the plasma at day 4 post-MI and GDF3 circulating levels were significantly associated with an increased risk of adverse remodeling 6-month post-MI (adjusted Odds Ratio (OR) = 1.76 [1.03 - 3.00], p = 0.037).Conclusions Our findings define a mechanism for the pro-fibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling following MI..
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Preprint| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
bioRxiv.org - (2021) vom: 03. Juni Zur Gesamtaufnahme - year:2021 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Masurkar, Nihar [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2021.05.31.21257816 |
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| PPN (Katalog-ID): |
XBI031896960 |
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| 520 | |a Abstract Background Myocardial infarction (MI) induces a repair response that ultimately generates a stable fibrotic scar. Although the scar prevents cardiac rupture, an excessive profibrotic response impairs optimal recovery.Objective To explore the regulation of fibroblasts proliferation through a paracrine action of cardiac stromal cells post-MIMethods We carried out a bioinformatic secretome analysis of cardiac stromal PW1+ cells isolated from normal and post-MI mouse hearts to identify novel secreted proteins. Functional assays were used to screen secreted proteins that promote fibroblast proliferation. The expressions of secreted proteins candidates were subsequently analyzed in mouse and human hearts and plasmas. The relation between levels of circulating protein candidates and adverse post-MI cardiac remodeling was examined in a cohort of 80 patients with a first ST-elevation MI and serial cardiac magnetic resonance imaging (MRI) evaluations.Results Cardiac stromal PW1+ cells undergo a change in paracrine behavior post-MI and secrete factors that promote fibroblast proliferation. Among these factors, growth differentiation factor 3 (GDF3), a member of the transforming growth factor-β family, was markedly upregulated in the ischemic hearts and induced fibroblast proliferation at high level. In humans, GDF3 was detected in the plasma at day 4 post-MI and GDF3 circulating levels were significantly associated with an increased risk of adverse remodeling 6-month post-MI (adjusted Odds Ratio (OR) = 1.76 [1.03 - 3.00], p = 0.037).Conclusions Our findings define a mechanism for the pro-fibrotic action of cardiac stromal cells through secreted cardiokines, such as GDF3, a candidate marker of adverse fibrotic remodeling following MI. | ||
| 700 | 1 | |a Bouvet, Marion |e verfasserin |4 aut | |
| 700 | 1 | |a Logeart, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Claude, Olivier |e verfasserin |4 aut | |
| 700 | 1 | |a Roux, Maguelonne |e verfasserin |4 aut | |
| 700 | 1 | |a Delacroix, Clément |e verfasserin |4 aut | |
| 700 | 1 | |a Bergerot, Damien |e verfasserin |4 aut | |
| 700 | 1 | |a Mercadier, Jean-Jacques |e verfasserin |4 aut | |
| 700 | 1 | |a Sirol, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Gellen, Barnabas |e verfasserin |4 aut | |
| 700 | 1 | |a Livrozet, Marine |e verfasserin |4 aut | |
| 700 | 1 | |a Fayol, Antoine |e verfasserin |4 aut | |
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