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Title: The role of Smad3 in myocardial infraction
Abstract:
Optimal infarct healing requires timely activation and resolution of inflammatory pathways and transition to fibrous tissue deposition. TGFB through activation of Smad-dependent or Smad-independent pathways regulates leukocyte recruitment, suppresses pro-inflammatory cytokine synthesis and promotes fibrosis by modulating fibroblast gene expression. Murine model of reperfused myocardial infarction was used to asses histological, molecular, echocardiographic and hemodynamic endpoints. Isolated fibroblasts from WT and Smad3-/- hearts were used in in vitro experiments. In the absence of injury Smad3 null hearts had comparable function and morphology to WT hearts. Smad3-/- animals had decreased neutrophil recruitment in the infarcted myocardium and showed decreased inflammatory gene expression. Although myofibroblast density was higher in Smad3-/- infarcts, the expression of the osteopontin was lower and MMP:TIMP balance had been changed suggesting an altered matrix synthesis profile. TGFB markedly upregulated TIMP-1 and TIMP-2 mRNA expression in WT, but not in S mad3-/- cardiac fibroblasts, suggesting that these effects of TGFB are Smad3 dependent. Smad3 gene disruption results in decreased remodeling and attenuated systolic and diastolic dysfunction following reperfused myocardial infarction. Smad3 signaling is not crucial for repression of inflammatory gene synthesis in healing ; infarcts, but critically regulates cardiac fibroblast behavior and extracellular matrix metabolism leading to favorable hemodynamic and morphological outcomes.
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Last modified:
Jul 19, 2022
In our library since:
Nov 21, 2012
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6
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All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/1108
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| Edition name | Date |
|---|---|
| ZB-105389 | Jul 19, 2022 |
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