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Updated: Jul 17, 2026
Modeling and Evaluation of Murine Diabetic Cardiomyopathy Model
Published on: November 29, 2024
Haptoglobin genotype determines myocardial infarct size in diabetic mice
Shany Blum1, Roy Asaf, Julia Guetta
1Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Objectives:
We sought to understand the importance of oxidative stress in explaining why the haptoglobin (Hp) genotype determines myocardial infarction (MI) size in diabetes mellitus (DM).
Background:
Two common alleles (1 and 2) exist at the Hp locus in humans. The Hp 2 allele is associated with increased MI size in individuals with DM. In vitro, the Hp 2 protein is associated with increased generation of oxidatively active iron, whereas the Hp 1 protein is associated with increased production of the antioxidant cytokine interleukin (IL)-10.
Methods:
Myocardial infarction was produced by myocardial ischemia-reperfusion (IR) in DM C57BL/6 mice carrying the Hp 1 or Hp 2 allele. Myocardial oxidative stress after IR was assessed using electrospray ionization mass spectrometry. Redox active iron and IL-10 were measured in the serum after IR.
Results:
Myocardial infarction size was significantly larger in Hp 2 mice as compared with Hp 1 mice (44.3 +/- 9.3% vs. 21.0 +/- 4.0%, p = 0.03), and these larger infarctions were associated with a significant increase in a panel of hydroxyl-eicosatetraenoic acids. Redox active iron was greater in Hp 2 mice (0.45 +/- 0.11 micromol/l vs. 0.14 +/- 0.05 micromol/l, p = 0.02), whereas IL-10 was greater in Hp 1 mice (85.8 +/- 12.9 pg/microl vs. 46.7 +/- 10.8 pg/microl, p = 0.04) after IR. Administration of an antioxidant (BXT-51072) to Hp 2 mice reduced myocardial injury after IR by more than 80% (p = 0.003), but no myocardial protection was provided by the antioxidant to Hp 1 mice.
Conclusions:
The increased MI size in DM Hp 2 mice occurring after IR may be due to increased oxidative stress.
