EVALUATION OF CARDIAC INVOLVEMENT IN THE MURINE MODEL OF FABRY DISEASE

MUCCI J; DE FRANCESCO, PN; FRITZ M; GONANO L; ROZENFELD PA; VILA PETROFF, M; RINALDI G

La Plata

Congreso; XVIII Reunión anual ISHR; 2010

International Society for Heart Research

Fabry disease is a rare X-linked lysosomal storage disorder that causes progressive cardiac affection. Preliminary results from our group have revealed alterations in hearts from murine model of Fabry disease (alfa-galactosidase A gen knockout) (RF) in comparison to wild type littermates (RWT). The aim of this work is to evaluate cardiac involvement by echocardiogram, force development from isolated papillary muscles and fractional shortening, intracellular calcium (indo-1 fluorescence) and frequency of cardiomyocytes using mice, 25-weeks of age (10 RF and 10 RWT). Contractility (dP/dt (max) was 2707 +/- 85 for RF and 3128 +/- 94 mmHg/seg for RWT. Shortening fraction was lower in RF (30 +/- 6%) as compared to RWT (47 +/- 2%). Papillary muscles from RF developed lower force than that from RWT (39.8 +/- 17.3 g vs 67.5 +/- 15.7 g, respectively, p<0,05). Isolated myocytes showed reduced basal contractility and lower calcium transient amplitude in comparison to RWT. In summary, cardiac dysfunction detected in this murine model is in accordance to clinical manifestations reported in human patients, and would be mediated by an alteration of calcium handling at the myocyte level. Thus, this model could be of use to understand pathophysiological mechanisms and to evaluate the response to novel treatment options.