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Cardiovasc Pathol. 2013 Nov-Dec;22(6):481-7. doi: 10.1016/j.carpath.2013.06.002. Epub 2013 Jul 27.

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

Author information

1
San Antonio Cardiovascular Proteomics Center, The University of Texas Health Science Center, San Antonio, TX, USA; Barshop Institute for Longevity and Aging Studies, and Division of Geriatrics, Gerontology and Palliative Medicine, The University of Texas Health Science Center, San Antonio, TX, USA.

Abstract

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.

KEYWORDS:

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

PMID:
23896047
PMCID:
PMC3965668
DOI:
10.1016/j.carpath.2013.06.002
[Indexed for MEDLINE]
Free PMC Article

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