Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction

James R. Heaberlin, Yonggang Ma, Jianhua Zhang, Seema S. Ahuja, Merry L. Lindsey, Ganesh V. Halade

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: Introduction of the yellow obese gene (Ay) into mice (KKAy) results in obesity and diabetes by 5 weeks of age. Methods: Using this model of type 2 diabetes, we evaluated male and female 6-to 8-month-old wild-type (WT, n=10) and KKAy (n=22) mice subjected to myocardial infarction (MI) and sacrificed at day (d) 7. Results: Despite similar infarct sizes (50%±4% for WT and 49%±2% for KKAy, P=not significant), the 7d post-MI survival was 70% (n=7/10) in WT mice and 45% (n=10/22) in KKAy mice (P<.05). Plasma glucose levels were 1.4-fold increased in KKAy mice at baseline compared to WT (P<.05). Glucose levels did not change in WT mice but decreased 38% in KKAy post-MI (P<.05). End-diastolic and end-systolic dimensions post-MI were smaller and fractional shortening improved in the KKAy (5%±1% in WT and 10%±2% in KKAy, P<.05 for all). The improved cardiac function in KKAy was accompanied by reduced macrophage numbers and collagen I and III levels (both P<.05). Griffonia (Bandeiraea) simplicifolia lectin-I staining for vessel density demonstrated fewer vessels in KKAy infarcts (5.9%±0.5%) compared to WT infarcts (7.3%±0.1%, P<.05). Conclusion: In conclusion, our study in KKAy mice revealed a paradoxical reduced post-MI survival but improved cardiac function through reduced inflammation, extracellular matrix accumulation, and neovascularization in the infarct region. These results indicate a dual-role effect of obesity in the post-MI response.

Original languageEnglish (US)
Pages (from-to)481-487
Number of pages7
JournalCardiovascular Pathology
Volume22
Issue number6
DOIs
StatePublished - Jan 1 2013

Keywords

  • Diabetes
  • Extracellular matrix
  • Heart failure
  • Inflammation
  • Myocardial infarction
  • Obesity

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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