4.3 Article

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

期刊

CARDIOVASCULAR PATHOLOGY
卷 22, 期 6, 页码 481-487

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.carpath.2013.06.002

关键词

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

资金

  1. NIH/NHLBI HHSN [268201000036C (N01-HV-00244), HL051971, R01 HL075360]
  2. Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award [5I01BX000505]
  3. NIH-NCCAM [K99AT006704]

向作者/读者索取更多资源

Background: Introduction of the yellow obese gene (A(y)) 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. (C) 2013 Elsevier Inc. All rights reserved.

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