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Data · dataset · 2022

Hypoxia preconditioned mesenchymal stem cells prevent cardiac fibroblast activation and collagen production via leptin

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Aims: Activation of cardiac fibroblasts into myofibroblasts constitutes a key step in cardiac remodeling after myocardial infarction (MI), due to interstitial fibrosis.

Description

Mesenchymal stem cells (MSCs) have been shown to improve post-MI remodeling an effect that is enhanced by hypoxia preconditioning (HPC). Leptin has been shown to promote cardiac fibrosis.

The expression of leptin is significantly increased in MSCs after HPC, but it is unknown whether leptin contributes to MSC therapy or the fibrosis process. The objective of this study was to determine whether leptin secreted from MSCs modulates cardiac fibrosis.

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Methods

Cardiac fibroblast (CF) activation was induced by hypoxia (0.5% O2). The effects of MSCs on fibroblast activation were analyzed by co-culturing MSCs with CFs and detecting the expression of a-SMA, SM22a, and collagen IaI in CFs by western blot, immunofluorescence and Sirius red staining. In vivo MSCs antifibrotic effects on left ventricular remodeling were investigated using an acute MI model involving permanent ligation of the left anterior descending coronary artery.

Results: Co-cultured MSCs decreased fibroblast activation and HPC enhanced the effects. Leptin deficit MSCs from Ob/Ob mice did not decrease fibroblast activation. Consistent with this, H-MSCs significantly inhibited cardiac fibrosis after MI and mediated decreased expression of TGF-b/Smad2 and MRTF-A in CFs.

These effects were again absent in leptin-deficient MSCs. Conclusion: Our data demonstrate that activation of cardiac fibroblast was inhibited by MSCs in a manner that was leptin-dependent. The mechanism may involve blocking TGF-b/Smad2 and MRTF-A signal pathway.

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Topics

Stated by source
Basic medicine
Inferred from text
Cardiac remodeling 75% · Heart 65% · Myocardial infarction 75%
Provenance · 1 source records, 11 field assertions
SourceKeyLast seenRaw
DataCite10.5061/dryad.sf7m0cg9d12 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · DataCiteconnector:datacite@1.0.0/data/attributes/rightsList
byte_sizesource · DataCiteconnector:datacite@1.0.0
concepts[anatomy].local:anatomy:heartenrichment · DataCitekeyword-concept-rules@1.0.0title+description (65%)
concepts[disease].local:disease:cardiac-remodelingenrichment · DataCitekeyword-concept-rules@1.0.0title+description (75%)
concepts[disease].local:disease:myocardial-infarctionenrichment · DataCitekeyword-concept-rules@1.0.0title+description (75%)
concepts[field].fos:basic-medicinesource · DataCiteconnector:datacite@1.0.0
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