Leptin deficiency enhances myocardial necrosis and lethality in a murine model of viral myocarditis

Life Sci. 2004 Aug 6;75(12):1435-47. doi: 10.1016/j.lfs.2004.03.012.

Abstract

To investigate the role of leptin in the development of viral myocarditis and cardiac necrosis, we used a murine model of viral myocarditis. We intraperitoneally injected encephalomyocarditis virus (500 plaque-forming units/mouse) for wild type C57 BL/6 mice (WT) and leptin-deficient ob/ob mice (OB) (n = 20 for each). Ten-day survival rate was 25% in OB, whereas it was 95% in WT. Heart weights on day 10 were significantly elevated in OB compared with those in WT (107.2 +/- 9.4 vs. 96.6 +/- 7.9 mg, n = 4 for each). Thymus weights were significantly diminished in OB compared with those in WT on days 6 and 10. Histological score (grade 1 to 4 according to the size of involved area) for myocardial necrosis were significantly higher in OB than in WT (1.5 +/- 0.5 vs. 0.8 +/- 0.5, n = 4 for each). On day 4, viral titer in hearts was significantly elevated in OB compared with that in WT (3.3 +/- 0.5 vs. 1.9 +/- 0.2 TCID50/mg, n = 3 for each). Comparative expression of TNF-alpha mRNA in hearts from OB were significantly increased compared with those in WT on day 7 (n = 3 for each). Natural killer cell activities in spleens from OB were significantly lower than from WT on day 4 (27 +/- 5 vs. 42 +/- 8%, n = 4 for each). Thus, leptin deficiency could enhance severity of myocardial necrosis and mortality due to viral myocarditis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Encephalomyocarditis virus*
  • Heart / virology
  • Histological Techniques
  • Killer Cells, Natural / immunology
  • Leptin / deficiency*
  • Mice
  • Mice, Mutant Strains
  • Myocarditis / metabolism*
  • Myocarditis / pathology
  • Myocarditis / virology*
  • Myocardium / pathology
  • Necrosis
  • Organ Size
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / immunology
  • Statistics, Nonparametric
  • Survival Analysis
  • Thymus Gland / pathology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Leptin
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha