Endocrine Abstracts (2010) 22 P137

FABP4 inhibitor strongly depresses cardiac function

Valéria Lamounier-Zepter1, Christiane Look1, Stefan Bornstein1 & Ingo Morano2

1University of Technology Dresden, Dresden, Germany; 2Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.

Adipocyte fatty acid binding protein (FABP4) is emerging as a novel risk marker for metabolic syndrome and atherosclerosis. In this context we recently showed that FABP4 released by human adipocytes suppresses cardiomyocyte contraction, thus suggesting a pathogenic role for FABP4 in the cardiac dysfunction in obesity. Since a new FABP4 inhibitor which competitively inhibits the binding of endogenous fatty acids to FABP4 was effective in the treatment of atherosclerosis and diabetes mellitus in mouse models, we investigated the cardiac effect of this FABP4 inhibitor using isolated cardiomyocytes and heart preparations in a Langendorff system. FABP4 inhibitor depresses cardiomyocyte contraction in vitro without attenuating Ca2+-levels. The inotropic negative effect of FABP4 inhibitor was concentration-dependent at a maximal effective concentration of 500 nmol/l. In Langendorff heart preparations, FABP4 inhibitor induced a dramatic effect on cardiac contractility leading to asystoly expressed by a total breakdown of left ventricular pressure after a small period of irregular cardiac contraction, without interfering in the electrocardiographic activity. Thus, FABP4 may be a novel therapeutic target for treating metabolic and cardiovascular complications of metabolic syndrome although other inhibitors lacking this dramatic deleterious effect on cardiac function must be developed.

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