Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure

Le résumé fourni par la source

Abstract The prevailing view of fibulin-4 deficient mice is that the cardiac phenotype is the result of aortic and/or valvular disease. In the present study, we have tested whether the cardiac phenotype is, at least in part, the consequence of primary cardiac effects of fibulin-4. We have found fibulin-4 expression to be activated throughout the myocardium in wildtype (fibulin-4+/+) C57Bl/6J;129 Sv mice subjected to transverse aortic constriction (TAC). In contrast, haploinsufficient fibulin-4+/R mice exposed to severe TAC do not show this increase in myocardial fibulin-4 expression, but display altered physical properties of myocardial tissue. Moreover, TAC-induced cardiac fibrosis, pulmonary congestion, and mortality are aggravated in fibulin-4+/R mice. In vitro investigations of myocardial tissue show that fibulin-4 deficiency results in cardiomyocyte hypertrophy, and a decreased beating frequency and contractile force. In conclusion, we demonstrate functions for fibulin-4 in cardiac homeostasis and show that reduced fibulin-4 expression drives myocardial disease in response to cardiac pressure overload, independent of aortic valvular pathology.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.