Calcineurin expression, activation, and function in cardiac pressure-overload hypertrophy.
Circulation
; 101(20): 2431-7, 2000 May 23.
Article
in En
| MEDLINE
| ID: mdl-10821822
ABSTRACT
BACKGROUND:
Vascular hypertension resulting in increased cardiac load is associated with left ventricular hypertrophy and is a leading predicator for progressive heart disease. The molecular signaling pathways that respond to increases in cardiac load are poorly understood. One potential regulator of the hypertrophic response is the calcium-sensitive phosphatase calcineurin. METHODS ANDRESULTS:
We showed that calcineurin enzymatic activity is increased 3. 2-fold in the heart in response to pressure-overload hypertrophy induced by abdominal aortic banding in the rat. Western blot analysis further demonstrates that calcineurin A (catalytic subunit) protein content and association with calmodulin are increased in response to pressure-overload hypertrophy. This increase in calcineurin protein content was prevented by administration of the calcineurin inhibitor cyclosporine A (CsA). CsA administration attenuated load-induced cardiac hypertrophy in a dose-dependent manner over a 14-day treatment protocol. CsA administration also partially reversed pressure-overload hypertrophy in aortic-banded rats after 14 days. CsA also attenuated the histological and molecular indexes of pressure-overload hypertrophy.CONCLUSIONS:
These data suggest that calcineurin is an important upstream regulator of load-induced hypertrophy.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiomegaly
/
Calcineurin
/
Hypertension
Type of study:
Guideline
Limits:
Animals
Language:
En
Journal:
Circulation
Year:
2000
Type:
Article
Affiliation country:
United States