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Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury

Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involv...

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Autores principales: Lin, Han-Bin, Cadete, Virgilio J. J., Sra, Bikramjit, Sawicka, Jolanta, Chen, Zhicheng, Bekar, Lane K., Cayabyab, Francisco, Sawicki, Grzegorz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131446/
https://www.ncbi.nlm.nih.gov/pubmed/25147815
http://dx.doi.org/10.1155/2014/810371
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author Lin, Han-Bin
Cadete, Virgilio J. J.
Sra, Bikramjit
Sawicka, Jolanta
Chen, Zhicheng
Bekar, Lane K.
Cayabyab, Francisco
Sawicki, Grzegorz
author_facet Lin, Han-Bin
Cadete, Virgilio J. J.
Sra, Bikramjit
Sawicka, Jolanta
Chen, Zhicheng
Bekar, Lane K.
Cayabyab, Francisco
Sawicki, Grzegorz
author_sort Lin, Han-Bin
collection PubMed
description Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2) in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological) conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury.
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spelling pubmed-41314462014-08-21 Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury Lin, Han-Bin Cadete, Virgilio J. J. Sra, Bikramjit Sawicka, Jolanta Chen, Zhicheng Bekar, Lane K. Cayabyab, Francisco Sawicki, Grzegorz Biomed Res Int Research Article Matrix metalloproteinases (MMPs) significantly contribute to ischemia reperfusion (I/R) injury, namely, by the degradation of contractile proteins. However, due to the experimental models adopted and lack of isoform specificity of MMP inhibitors, the cellular source and identity of the MMP(s) involved in I/R injury remain to be elucidated. Using isolated adult rat cardiomyocytes, subjected to chemically induced I/R-like injury, we show that specific inhibition of MMP-2 expression and activity using MMP-2 siRNA significantly protected cardiomyocyte contractility from I/R-like injury. This was also associated with increased expression of myosin light chains 1 and 2 (MLC1/2) in comparison to scramble siRNA transfection. Moreover, the positive effect of MMP-2 siRNA transfection on cardiomyocyte contractility and MLC1/2 expression levels was also observed under control conditions, suggesting an important additional role for MMP-2 in physiological sarcomeric protein turnover. This study clearly demonstrates that intracellular expression of MMP-2 plays a significant role in sarcomeric protein turnover, such as MLC1 and MLC2, under aerobic (physiological) conditions. In addition, this study identifies intracellular/autocrine, cardiomyocyte-produced MMP-2, rather than paracrine/extracellular, as responsible for the degradation of MLC1/2 and consequent contractile dysfunction in cardiomyocytes subjected to I/R injury. Hindawi Publishing Corporation 2014 2014-07-24 /pmc/articles/PMC4131446/ /pubmed/25147815 http://dx.doi.org/10.1155/2014/810371 Text en Copyright © 2014 Han-Bin Lin et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Lin, Han-Bin
Cadete, Virgilio J. J.
Sra, Bikramjit
Sawicka, Jolanta
Chen, Zhicheng
Bekar, Lane K.
Cayabyab, Francisco
Sawicki, Grzegorz
Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title_full Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title_fullStr Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title_full_unstemmed Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title_short Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
title_sort inhibition of mmp-2 expression with sirna increases baseline cardiomyocyte contractility and protects against simulated ischemic reperfusion injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131446/
https://www.ncbi.nlm.nih.gov/pubmed/25147815
http://dx.doi.org/10.1155/2014/810371
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