A neutralizing leptin receptor antibody mitigates hypertrophy and hemodynamic dysfunction in the postinfarcted rat heart. Am J Physiol Heart Circ Physiol 2008 Jul;295(1):H441-6
Date
05/13/2008Pubmed ID
18469142DOI
10.1152/ajpheart.91537.2007Scopus ID
2-s2.0-49849103205 (requires institutional sign-in at Scopus site) 54 CitationsAbstract
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.
Author List
Purdham DM, Rajapurohitam V, Zeidan A, Huang C, Gross GJ, Karmazyn MMESH terms used to index this publication - Major topics in bold
AnimalsAntibodies
Disease Models, Animal
Extracellular Matrix
Hemodynamics
Hypertrophy, Left Ventricular
Leptin
Male
Myocardial Infarction
Myocardium
Rats
Rats, Sprague-Dawley
Receptors, Leptin
Time Factors
Ventricular Dysfunction, Left
Ventricular Pressure
Ventricular Remodeling
