EVALUATION OF CARDIAC INVOLVEMENT IN THE MURINE MODEL OF FABRY DISEASE

MUCCI J.; DE FRANCESCO P.; FRITZ M.; GONANO L.; ROZENFELD P.; VILA PETROFF M.; RINALDI G.

La Plata

Congreso; XVIII Meeting ISHR LATIN AMERICAN SECTION; 2010

Fabry disease is a rare X-linked lysosomal storage disorder that causes progressivecardiac affection. Preliminary results from our group have revealed a lowercontractility, higher distensibility and disarray of myocardium architecture in heartsfrom murine model of Fabry disease (alfa-galactosidase A gen knockout) (RF) incomparison to wild type littermates (RWT).The aim of this work is to evaluate cardiac involvement by echocardiogram and forcedevelopment from isolated papillary muscles and cardiomyocytes.Mice, 25-weeks of age (10 RF and 10 RWT) were subjected to echocardiogram andcontractility assessments. Then the hearts were excised and force development bypapillary muscles was measured. Also, fractional shortening, intracellular calcium(indo-1 fluorescence) and frequency were assessed in isolated cardiomyocytes.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 gvs 67.5 +/- 15.7 g, respectively, p<0,05). Isolated myocytes showed reduced basalcontractility and lower calcium transient amplitude in comparison to RWT.In summary, cardiac dysfunction detected in this murine model is in accordance toclinical manifestations reported in human patients, and would be mediated by analteration of calcium handling at the myocyte level. Thus, this model could be of use tounderstand pathophysiological mechanisms and to evaluate the response to noveltreatment options.