Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury
Joint Authors
Cayabyab, Francisco
Bekar, Lane K.
Chen, Zhicheng
Cadete, Virgilio J. J.
Lin, Han-Bin
Sawicki, Grzegorz
Sawicka, Jolanta
Sra, Bikramjit
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-07-24
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Lin, Han-Bin& Cadete, Virgilio J. J.& Sra, Bikramjit& Sawicka, Jolanta& Chen, Zhicheng& Bekar, Lane K.…[et al.]. 2014. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury. BioMed Research International،Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-499903
Modern Language Association (MLA)
Lin, Han-Bin…[et al.]. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury. BioMed Research International No. 2014 (2014), pp.1-11.
https://search.emarefa.net/detail/BIM-499903
American Medical Association (AMA)
Lin, Han-Bin& Cadete, Virgilio J. J.& Sra, Bikramjit& Sawicka, Jolanta& Chen, Zhicheng& Bekar, Lane K.…[et al.]. Inhibition of MMP-2 Expression with siRNA Increases Baseline Cardiomyocyte Contractility and Protects against Simulated Ischemic Reperfusion Injury. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-11.
https://search.emarefa.net/detail/BIM-499903
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-499903