Calcium desensitizer catechin reverses diastolic dysfunction in mice with restrictive cardiomyopathy.

Abstract

Diastolic dysfunction refers to an impaired relaxation and an abnormality in ventricular blood filling during diastole while systolic function is preserved. Cardiac myofibril hypersensitivity to Ca(2+) is a major factor that causes impaired relaxation of myocardial cells. The present study investigates the effect of the green tea extract catechins on myofibril calcium desensitization and restoration of diastolic function in a restrictive cardiomyopathy (RCM) mouse model with cardiac troponin mutations. Wild type (WT) and RCM mice were treated daily with catechin (epigallocatechin-3-gallate, EGCg, 50 mg/kg body weight) for 3 months. Echocardiography and cell based assays were performed to measure cardiac structure and flow-related variables including chamber dimensions, fraction shortening, trans-mitral flow patterns in the experimental mice. In addition, myocyte contractility and calcium dynamics were measured in WT and RCM cardiomyocytes treated in vitro with 5 μM EGCg. Our data indicated that RCM mice treated with EGCg showed an improved diastolic function while systolic function remained unchanged. At the cellular level, sarcomere relaxation and calcium decay were accelerated in RCM myocardial cells treated with EGCg. These results suggest that catechin is effective in reversing the impaired relaxation in RCM myocardial cells and rescuing the RCM mice with diastolic dysfunction.

• Authors: Lei Zhang, Changlong Nan, Yuan Chen, Jie Tian, Pierre-Yves Jean-Charles, Cecile Getfield, Xiaoqing Wang, Xupei Huang
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 573 Pg. 69-76 (May 01 2015) ISSN: 1096-0384 [Electronic] United States
• PMID: 25813360 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Troponin I
• Catechin
• epigallocatechin gallate
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Cardiomyopathy, Restrictive (metabolism, pathology, physiopathology)
• Catechin (analogs & derivatives, pharmacology)
• Cell Size (drug effects)
• Diastole (drug effects)
• Electrocardiography
• Mice, Transgenic
• Myocytes, Cardiac (drug effects, physiology)
• Sarcomeres (drug effects, physiology)
• Troponin I (genetics)