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There is currently no therapy to limit the development of cardiac fibrosis and consequent heart failure. We have recently shown that cardiac fibrosis post-myocardial infarction (MI) can be regulated by resident cardiac cells with a fibrogenic signature and identified by the expression of PW1 (Peg3). Here we identify αV-integrin (CD51) as an essential regulator of cardiac PW1 cells fibrogenic behavior. We used transcriptomic and proteomic approaches to identify specific cell-surface markers for cardiac PW1 cells and found that αV-integrin (CD51) was expressed in almost all cardiac PW1 cells (93% ± 1%), predominantly as the αVβ1 complex. αV-integrin is a subunit member of the integrin family of cell adhesion receptors and was found to activate complex of latent transforming growth factor beta (TGFβ at the surface of cardiac PW1 cells. Pharmacological inhibition of αV-integrin reduced the profibrotic action of cardiac PW1CD51 cells and was associated with improved cardiac function and animal survival following MI coupled with a reduced infarct size and fibrotic lesion. These data identify a targetable pathway that regulates cardiac fibrosis in response to an ischemic injury and demonstrate that pharmacological inhibition of αV-integrin could reduce pathological outcomes following cardiac ischemia.
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http://dx.doi.org/10.1038/s41598-020-68223-8 | DOI Listing |
Circulation
December 2024
School of Life Science and Technology (S.K., D.D., M.Y., Y.S., T.F., Z.J., J.M., C.L., X.L., H.Z.).
Background: Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments. (paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.
View Article and Find Full Text PDFCells
May 2024
Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London SE1 1UL, UK.
In the original publication [...
View Article and Find Full Text PDFCells
December 2022
Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King's College London, Guy's Campus, London SE1 1UL, UK.
We have previously shown that skeletal muscle-derived Sca-1/PW1/Pax7 interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL/6 mice.
View Article and Find Full Text PDFCirculation
February 2023
Paris Cardiovascular Research Center, INSERM (N.M., M.B., C.J., F.D., O.C., C.D., E.R., G.M., D.S., M.V., J.-S.H.), Université de Paris, Cité' France.
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 by promoting the development of noncontractile fibrotic areas. The mechanisms that lead to cardiac fibrosis are diverse and incompletely characterized.
View Article and Find Full Text PDFForensic Sci Int
August 2022
Indiana University, Department of Criminal Justice, USA. Electronic address:
Despite contemporary media portrayals, violent crime has continued to decrease in recent decades. Consistent with traditional types of violent crime (e.g.
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