Macrophages modulate cardiac function in lipotoxic cardiomyopathy.
Authors Schilling JD, Machkovech HM, Kim AH, Schwendener R, Schaffer JE
Submitted By Jean Schaffer on 4/15/2014
Status Published
Journal American journal of physiology. Heart and circulatory physiology
Year 2012
Date Published 12/1/2012
Volume : Pages 303 : H1366 - H1373
PubMed Reference 23042950
Abstract Diabetes is associated with myocardial lipid accumulation and an increased risk
of heart failure. Although cardiac myocyte lipid overload is thought to
contribute to the pathogenesis of cardiomyopathy in the setting of diabetes, the
mechanism(s) through which this occurs is not well understood. Increasingly,
inflammation has been recognized as a key pathogenic feature of lipid excess and
diabetes. In this study, we sought to investigate the role of inflammatory
activation in the pathogenesis of lipotoxic cardiomyopathy using the a-myosin
heavy chain promoter-driven long-chain acylCoA synthetase 1 (MHC-ACS) transgenic
mouse model. We found that several inflammatory cytokines were upregulated in
the myocardium of MHC-ACS mice before the onset of cardiac dysfunction, and this
was accompanied by macrophage infiltration. Depletion of macrophages with
liposomal clodrolip reduced the cardiac inflammatory response and improved
cardiac function. Thus, in this model of lipotoxic cardiac injury, early
induction of inflammation and macrophage recruitment contribute to adverse
cardiac remodeling. These findings have implications for our understanding of
heart failure in the setting of obesity and diabetes.

Investigators with authorship
Jean SchafferWashington University in St Louis