title: Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: James R
authors.initials: JR
authors.lastname: Heaberlin
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Ma
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Seema S
authors.initials: SS
authors.lastname: Ahuja
authors.forename: Merry L
authors.initials: ML
authors.lastname: Lindsey
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D001786:Blood Glucose; D024042:Collagen Type I; D024061:Collagen Type III
keywords: Diabetes; Extracellular matrix; Heart failure; Inflammation; Myocardial infarction; Obesity
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