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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/H441    most recent 91537.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Purdham, D. M. Articles by Karmazyn, M. PubMed PubMed Citation Articles by Purdham, D. M. Articles by Karmazyn, M.

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A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart

¹Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada; and ²Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin

Submitted 31 December 2007 ; accepted in final form 6 May 2008

The 16 kDa adipokine leptin has been shown to exert direct hypertrophic effects on cultured cardiomyocytes although its role as an endogenous contributor to postinfarction remodeling and heart failure has not been determined. We therefore investigated the effect of leptin receptor blockade in vivo on hemodynamic function and cardiac hypertrophy following coronary artery ligation (CAL). Cardiac function and biochemical parameters were measured in rats subjected to 7 or 28 days of left main CAL in the presence and absence of a leptin receptor antibody. Animals subjected to an identical treatment in which the artery was not tied served as sham-operated controls. CAL produced myocardial hypertrophy, which was most pronounced 28 days postinfarction as demonstrated by increases in both left ventricular weight-to-body weight ratio and atrial natriuretic peptide gene expression, both of which were abrogated by leptin receptor antagonism. Leptin receptor blockade also significantly improved left ventricular systolic function, attenuated the increased left ventricular end-diastolic pressure, and reduced the expression of genes associated with extracellular matrix remodeling 28 days following CAL. In conclusion, the ability of a leptin receptor-neutralizing antibody to improve cardiac function offers evidence that endogenous leptin contributes to cardiac hypertrophy following CAL. The possibility exists that targeting the myocardial leptin receptor represents a viable and novel approach toward attenuating postinfarction remodeling.

myocardial infarction; leptin receptor blockade