Gender differences in adiponectin modulation of cardiac remodeling in mice deficient in endothelial nitric oxide synthase

Authors

  • Jorge L. Durand,

    1. Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461
    Current affiliation:
    1. Corbett Accel Healthcare Group, 220 E 42nd Street, New York, NY 10017.
    Search for more papers by this author
  • Andrea R. Nawrocki,

    1. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461
    Current affiliation:
    1. Merck Research Laboratories, 126 E Lincoln Ave, RY80Y-150/1D51 Rahway, NJ 07065-0900.
    Search for more papers by this author
  • Philipp E. Scherer,

    1. Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Touchstone Diabetes Center, Departments of Internal Medicine and Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas
    Search for more papers by this author
  • Linda A. Jelicks

    Corresponding author
    1. Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461
    2. Gruss Magnetic Resonance Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    • Gruss Magnetic Resonance Research Center, Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461.
    Search for more papers by this author

Abstract

Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular disease, a leading cause of death. Alterations in endothelial nitric oxide synthase (eNOS), an enzyme involved in regulating vascular tone, and in adiponectin, an adipocyte-derived secretory factor, are associated with cardiac remodeling. Deficiency of eNOS is associated with hypertension and LVH. Adiponectin exhibits vaso-protective, anti-inflammatory, and anti-atherogenic properties. We hypothesized that increased levels of adiponectin would alleviate cardiac pathology resulting from eNOS deficiency, while decreased levels of adiponectin would exacerbate the pathology. Male and female mice, deficient in eNOS, and either lacking or over-expressing adiponectin, were fed high fat diet (HFD) or normal chow. Cardiac magnetic resonance imaging was performed to serially assess heart morphology and function up to 40 weeks of age. Thirty-two weeks of HFD feeding led to significantly greater LV mass in male mice deficient in eNOS and either lacking or over-expressing adiponectin. Heart function was significantly reduced when the mice were deficient in either eNOS, adiponectin or both eNOS and adiponectin; for female mice, heart function was only reduced when both eNOS and adiponectin were lacking. Thus, while over-expression of adiponectin in the eNOS deficient HFD fed male mice preserved function at the expense of significantly increased LV mass, female mice were protected from decreased function and increased LVH by over-expression of adiponectin. Our results demonstrate a sexual dimorphism in response of the heart to alterations in eNOS and adiponectin during high fat feeding and suggest that adiponectin might require eNOS for some of its metabolic effects. J. Cell. Biochem. 113: 3276–3287, 2012. © 2012 Wiley Periodicals, Inc.

Ancillary