Calcineurin inhibitor attenuates cardiac hypertrophy due to energy metabolic disorder.
BACKGROUND
Several studies have shown that calcineurin may play a critical role in the signalling of cardiac hypertrophy in various experimental models.


OBJECTIVE
To elucidate whether calcineurin is involved in cardiac hypertrophy due to energy metabolic disorder by using the juvenile visceral steatosis (JVS) mouse, which is a murine model of systemic carnitine deficiency.


RESULTS
Cardiac hypertrophy in JVS mice (C3H strain) progresses gradually after birth and is present until eight weeks of age. In this study, calcineurin activity in JVS mice increased significantly at four weeks of age (the developing stage of cardiac hypertrophy) compared with age-matched control mice. Treatment with calcineurin inhibitor FK506 (0.5 or 1.0 mg/kg/day) from the age of four to eight weeks attenuated cardiac hypertrophy without beneficially affecting cardiac function. Gene expression, accompanied by cardiac hypertrophy, was also suppressed by the FK506 treatment.


CONCLUSIONS
The activation of calcineurin is involved in the development of cardiac hypertrophy in the JVS mouse, and calcineurin inhibition may be useful for reducing cardiac hypertrophy.
Kamiya
H
H
Internal Medicine II, Nagoya University School of Medicine, 67 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Okumura
K
K
Ito
M
M
Saburi
Y
Y
Tomida
T
T
Hayashi
K
K
Matsui
H
H
Hayakawa
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002100:Cachexia / Q000139:chemically induced; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism; D065095:Calcineurin Inhibitors; D006332:Cardiomegaly / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003920:Diabetes Mellitus / Q000139:chemically induced; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006973:Hypertension / Q000139:chemically induced; D007239:Infections / Q000139:chemically induced; D008661:Metabolism, Inborn Errors / Q000150:complications*; D051379:Mice; D008809:Mice, Inbred C3H; D009206:Myocardium / Q000473:pathology; D012016:Reference Values; D051437:Renal Insufficiency / Q000139:chemically induced; D016559:Tacrolimus / Q000009:adverse effects / Q000494:pharmacology*
D065095:Calcineurin Inhibitors; D019703:Calcineurin; D016559:Tacrolimus