Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia

Ching Hui Weng, Fa Po Chung, Yao Chang Chen, Shien Fong Lin, Po Hsun Huang, Terry B J Kuo, Wei Hsuan Hsu, Cheng Wen Su, Yen Ling Sung, Yenn Jiang Lin, Shih Lin Chang, Li Wei Chou, Hung I. Yeh, Yi-Jen Chen, Yi Ren Hong, Shih Ann Chen, Yu Feng Hu

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

Observational studies have established a strong association between matrix metalloproteinase-9 (MMP-9) and ventricular arrhythmia. However, whether MMP-9 has a causal link to ventricular arrhythmia, as well as the underlying mechanism, remains unclear. Here, we investigated the mechanistic involvement of myocardial MMP-9 in the pathophysiology of ventricular arrhythmia. Increased levels of myocardial MMP-9 are linked to ventricular arrhythmia attacks after angiotensin II (Ang II) treatment. MMP-9-deficient mice were protected from ventricular arrhythmia. Increased expressions of protein kinase A (PKA) and ryanodine receptor phosphorylation at serine 2808 (pS2808) were correlated with inducible ventricular arrhythmia. MMP-9 deficiency consistently prevented PKA and pS2808 increases after Ang II treatment and reduced ventricular arrhythmia. Calcium dynamics were examined via confocal imaging in isolated murine cardiomyocytes. MMP-9 inhibition prevents calcium leakage from the sarcoplasmic reticulum and reduces arrhythmia-like irregular calcium transients via protein kinase A and ryanodine receptor phosphorylation. Human induced pluripotent stem cell-derived cardiomyocytes similarly show that MMP-9 inhibition prevents abnormal calcium leakage. Myocardial MMP-9 inhibition prevents ventricular arrhythmia through pleiotropic effects, including the modulation of calcium homeostasis and reduced calcium leakage.
原文英語
文章編號38894
期刊Scientific Reports
6
DOIs
出版狀態已發佈 - 十二月 14 2016

指紋

Matrix Metalloproteinase 9
Cardiac Arrhythmias
Calcium
Cyclic AMP-Dependent Protein Kinases
Ryanodine Receptor Calcium Release Channel
Phosphorylation
Cardiac Myocytes
Angiotensin II
Serine
Induced Pluripotent Stem Cells
Sarcoplasmic Reticulum
Observational Studies
Homeostasis

ASJC Scopus subject areas

  • General

引用此文

Weng, C. H., Chung, F. P., Chen, Y. C., Lin, S. F., Huang, P. H., Kuo, T. B. J., ... Hu, Y. F. (2016). Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia. Scientific Reports, 6, [38894]. https://doi.org/10.1038/srep38894

Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia. / Weng, Ching Hui; Chung, Fa Po; Chen, Yao Chang; Lin, Shien Fong; Huang, Po Hsun; Kuo, Terry B J; Hsu, Wei Hsuan; Su, Cheng Wen; Sung, Yen Ling; Lin, Yenn Jiang; Chang, Shih Lin; Chou, Li Wei; Yeh, Hung I.; Chen, Yi-Jen; Hong, Yi Ren; Chen, Shih Ann; Hu, Yu Feng.

於: Scientific Reports, 卷 6, 38894, 14.12.2016.

研究成果: 雜誌貢獻文章

Weng, CH, Chung, FP, Chen, YC, Lin, SF, Huang, PH, Kuo, TBJ, Hsu, WH, Su, CW, Sung, YL, Lin, YJ, Chang, SL, Chou, LW, Yeh, HI, Chen, Y-J, Hong, YR, Chen, SA & Hu, YF 2016, 'Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia', Scientific Reports, 卷 6, 38894. https://doi.org/10.1038/srep38894
Weng, Ching Hui ; Chung, Fa Po ; Chen, Yao Chang ; Lin, Shien Fong ; Huang, Po Hsun ; Kuo, Terry B J ; Hsu, Wei Hsuan ; Su, Cheng Wen ; Sung, Yen Ling ; Lin, Yenn Jiang ; Chang, Shih Lin ; Chou, Li Wei ; Yeh, Hung I. ; Chen, Yi-Jen ; Hong, Yi Ren ; Chen, Shih Ann ; Hu, Yu Feng. / Pleiotropic Effects of Myocardial MMP-9 Inhibition to Prevent Ventricular Arrhythmia. 於: Scientific Reports. 2016 ; 卷 6.
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