Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/10390
Role of Calcineurin in the development of cardiac hypertrophy
CNIC Scientific Retreat. 2012
Previous studies have shown that the Calcineurin (CN)/NFAT signalling pathway is an established important regulator of cardiac hypertrophy. However, most studies are based on gain- and loss-of-function initiated at or before birth, and there are no detailed studies about the role of this pathway in the progression of pathological cardiac remodelling during adulthood. To investigate the role of CN in the progression of disease we have analyzed the effect of cyclosporin A (CsA), a pharmacological CN inhibitor, on angiotensin II (AngII)-induced hypertension and cardiac hypertrophy in mice. Our results show that although CsA treatment does not alter the AngII-induced hypertension, it blocks the increase of cardiac mass, ventricular Wall thickness and cardiomyocyte size when hypertrophy is established (21 days after AngII infusion). Unexpectedly, AngII infusion induces hypertrophy as early as three days and this effect is also inhibited by CsA. Interestingly, CsA impairs cardiac function and has no effect on AngII-induced fibrosis. A complementary analysis based on the inducible genetic deletion of CN in heart just before the induction of hypertrophy indicates that CN deficiency results in a clear reduction of hypertrophy accompanied by a blockade of AngII-induced fibrosis. Furthermore, CN deficient mice, but not CsA-treated mice, do not develop systolic dysfunction
CNIC Scientific Retreat. Madrid, 23-24 Nov. 2012
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