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• W2942282623 abstract "Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exo TIMP2 ) on the MI rat model. The huc-exo TIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exo TIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exo TIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exo TIMP2 pretreatment could inhibit H 2 O 2 -mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGF β -induced MMP2, MMP9, and α -SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exo TIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exo TIMP2 , indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exo TIMP2 abrogated the protective effects. Taken together, huc-exo TIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway." @default.
• W2942282623 created "2019-05-03" @default.
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• W2942282623 date "2019-04-28" @default.
• W2942282623 modified "2023-10-18" @default.
• W2942282623 title "Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway" @default.
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• W2942282623 doi "https://doi.org/10.1155/2019/1958941" @default.
• W2942282623 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6512021" @default.
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