title: 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: Division of Cardiology, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA; Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, FL 33431, USA.
authors: Changlong
authors: C
authors: Nan
authors: Division of Cardiology, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors: Yuan
authors: Y
authors: Chen
authors: Division of Cardiology, Children's Hospital, Chongqing Medical University, Chongqing, China.
authors: Jie
authors: J
authors: Tian
authors: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA.
authors: Pierre-Yves
authors: PY
authors: Jean-Charles
authors: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA.
authors: Cecile
authors: C
authors: Getfield
authors: Department of Biomedical Science, Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA.
authors: Xiaoqing
authors: X
authors: Wang
authors: Division of Cardiology, Children's Hospital, Chongqing Medical University, Chongqing, China; Department of Biomedical Science, Charles E. Schmidt College of Medicine, Boca Raton, FL 33431, USA; Center for Molecular Biology and Biotechnology, Florida Atlantic University, Boca Raton, FL 33431, USA. Electronic address: xhuang@fau.edu.
authors: Xupei
authors: X
authors: Huang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002313:Cardiomyopathy, Restrictive / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D003971:Diastole / Q000187:drug effects*; D004562:Electrocardiography; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D012518:Sarcomeres / Q000187:drug effects / Q000502:physiology; D019210:Troponin I / Q000235:genetics
chemical_list: D019210:Troponin I; D002392:Catechin; C045651:epigallocatechin gallate; D002118:Calcium
keywords: Calcium desensitizer; Calcium hypersensitivity; Catechins; Diastolic dysfunction; Myocardial cells; Transgenic mice