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 Citations (Scopus)

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

Fingerprint

Myocardial Infarction
Mortality
Obesity
Glucose
Type 2 Diabetes Mellitus
Extracellular Matrix
Collagen
Macrophages
Staining and Labeling
Inflammation
Genes
Griffonia simplicifolia lectins

Keywords

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

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction. / Heaberlin, James R.; Ma, Yonggang; Zhang, Jianhua; Ahuja, Seema S.; Lindsey, Merry L; Halade, Ganesh V.

In: Cardiovascular Pathology, Vol. 22, No. 6, 01.01.2013, p. 481-487.

Research output: Contribution to journalArticle

Heaberlin, James R. ; Ma, Yonggang ; Zhang, Jianhua ; Ahuja, Seema S. ; Lindsey, Merry L ; Halade, Ganesh V. / Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction. In: Cardiovascular Pathology. 2013 ; Vol. 22, No. 6. pp. 481-487.
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T1 - Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction

AU - Heaberlin, James R.

AU - Ma, Yonggang

AU - Zhang, Jianhua

AU - Ahuja, Seema S.

AU - Lindsey, Merry L

AU - Halade, Ganesh V.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

AB - 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.

KW - Diabetes

KW - Extracellular matrix

KW - Heart failure

KW - Inflammation

KW - Myocardial infarction

KW - Obesity

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