Premium
D‐4F attenuates calcineurin‐induced cardiac hypertrophy and heart failure
Author(s) -
Wei Na,
Ge Zhidong,
Du Jianhai,
An Jianzhong,
Warltier David C,
Pritchard Kirkwood A,
Shi Yang
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.812.1
Subject(s) - calcineurin , medicine , heart failure , endocrinology , muscle hypertrophy , nfat , fibrosis , cardiac function curve , cardiology , chemistry , transplantation
D‐4F, an apolipoprotein A‐I mimetic, has been shown to improve vascular function in atherosclerosis, diabetes and a variety of inflammatory diseases. However, the potential benefits of D‐4F in cardiac hypertrophy remain unknown. Calcineurin is a calcium‐sensitive type IIB phosphatase, which has been demonstrated to play a role in human heart hypertrophy. Transgenic Calcineurin A (CnA‐TG) mouse is an established murine model of cardiac hypertrophy and heart failure. Here, we investigate whether D‐4F attenuates cardiac hypertrophy and heart failure in CnA‐TG mice. CnA‐TG and wild type mice, immediately after weaning were treated with PBS or D‐4F (1 or 3 mg/kg/day) for 8 weeks. D‐4F dose‐dependently reduced ventricular mass to body weight ratios, cardiomyocyte cell size as well as interstitial fibrosis. Echocardiography revealed that D‐4F significantly prevented left ventricular wall thickness, elevated mitral E/A ratios, decreased E wave deceleration times and cardiac arrhythmias in CnA‐TG mice. Additionally, real‐time PCR shows that D‐4F decreased expression of ANP, β‐MHC; increased expression of sarcoplasmic reticulum Ca 2+ ATPase and c‐fos. Cardiac hemodynamics, plasma lipids and lipoprotein levels were essentially unchanged among the groups. In conclusion, D‐4F effectively reduces cardiac hypertrophy to protect the hearts of CnA‐TG mice from programmed failure.