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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.

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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.



Introduction of the yellow obese gene (A(y)) into mice (KKAy) results in obesity and diabetes by 5 weeks of age.


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.


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).


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.


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

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