Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the AktSfrp2 Pathway
Joint Authors
Xu, Yawei
Ni, Jing
Liu, Xijun
Yin, Yiheng
Zhang, Peiyu
Liu, Zheng
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-19, 19 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-04-28
Country of Publication
Egypt
No. of Pages
19
Main Subjects
Abstract EN
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-exoTIMP2) on the MI rat model.
The huc-exoTIMP2 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-exoTIMP2 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-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models.
In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs).
Besides that, huc-exoTIMP2 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-exoTIMP2, indicating a mechanistic basis of its action.
Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects.
Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.
American Psychological Association (APA)
Ni, Jing& Liu, Xijun& Yin, Yiheng& Zhang, Peiyu& Xu, Yawei& Liu, Zheng. 2019. Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the AktSfrp2 Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-19.
https://search.emarefa.net/detail/BIM-1202431
Modern Language Association (MLA)
Ni, Jing…[et al.]. Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the AktSfrp2 Pathway. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-19.
https://search.emarefa.net/detail/BIM-1202431
American Medical Association (AMA)
Ni, Jing& Liu, Xijun& Yin, Yiheng& Zhang, Peiyu& Xu, Yawei& Liu, Zheng. Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the AktSfrp2 Pathway. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-19.
https://search.emarefa.net/detail/BIM-1202431
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1202431