Cardiac tissue inhibitor of matrix metalloprotease 4 dictates cardiomyocyte contractility and differentiation of embryonic stem cells into cardiomyocytes: Road to therapy

International Journal of Cardiology
Pankaj ChaturvediSuresh C Tyagi

Abstract

TIMP4 (Tissue Inhibitors of Matrix Metalloprotease 4), goes down in failing hearts and mice lacking TIMP4 show poor regeneration capacity after myocardial infarction (MI). This study is based on our previous observation that administration of cardiac inhibitor of metalloproteinase (~TIMP4) attenuates oxidative stress and remodeling in failing hearts. Therefore, we hypothesize that TIMP4 helps in cardiac regeneration by augmenting contractility and inducing the differentiation of cardiac progenitor cells into cardiomyocytes. To validate this hypothesis, we transfected mouse cardiomyocytes with TIMP4 and TIMP4-siRNA and performed contractility studies in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyocytes. We evaluated the calcium channel gene serca2a (sarcoplasmic reticulum calcium ATPase2a) and mir122a which tightly regulates serca2a to explain the changes in contractility. We treated mouse embryonic stem cells with cardiac extract and cardiac extract minus TIMP4 (using TIMP4 monoclonal antibody) to examine the effect of TIMP4 on differentiation of cardiac progenitor cells. Contractility was augmented in the TIMP4 transfected cardiomyocytes as compared to siRNA-TIMP4 transfected cardiomyoc...Continue Reading

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Citations

Nov 27, 2015·Biological & Pharmaceutical Bulletin·Guping WangBainian Feng
Aug 28, 2015·Heart Failure Reviews·George H KunkelSuresh C Tyagi
May 12, 2016·Heart Failure Reviews·George H KunkelSuresh C Tyagi
Oct 27, 2016·Journal of Cellular and Molecular Medicine·Pankaj Chaturvedi, Suresh C Tyagi
May 1, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Nisha S GeorgeNelly Andarawis-Puri
Feb 9, 2021·Annals of Vascular Surgery·Syeda Anum ZahraMohamad Bashir

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