Haptoglobin genotype determines myocardial infarct size in diabetic mice.

Haptoglobin genotype determines myocardial infarct size in diabetic mice. Research Abstract Details 

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Haptoglobin genotype determines myocardial infarct size in diabetic mice. Abstract Text:

Shany Blum,Roy Asaf,Julia Guetta,Rachel Miller-Lotan,Rabea Asleh,Ran Kremer,Nina S Levy,Franklin G Berger,Doron Aronson,Xiaoming Fu,Renliang Zhang,Stanley L Hazen,Andrew P Levy,

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.

Haptoglobin genotype determines myocardial infarct size in diabetic mice. Publishing Authors By Initials

S Blum,R Asaf,J Guetta,R Miller-Lotan,R Asleh,R Kremer,NS Levy,FG Berger,D Aronson,X Fu,R Zhang,SL Hazen,AP Levy,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: oxidative stress research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: oxidative stress research

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Haptoglobin genotype determines myocardial infarct size in diabetic mice. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American College of Cardiology

VOLUME: 49

Page Numbers: 82-7

Journal Abbreviation: J. Am. Coll. Cardiol.

ISSN: 1558-3597

DAY: 13

MONTH: 12

YEAR: 2006

Haptoglobin genotype determines myocardial infarct size in diabetic mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8301365

Haptoglobin genotype determines myocardial infarct size in diabetic mice. Keywords Mesh Terms:

KEYWORDS: Oxidative Stress

MESH TERMS: metabolism

Chemical & Substance for Abstract: Haptoglobin genotype determines myocardial infarct size in diabetic mice. Information

Substance Name: Iron

Registry Number: 7439-89-6

Grant and Affiliation Information for Haptoglobin genotype determines myocardial infarct size in diabetic mice.

AFFILIATION: Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Country: United States

AGENCY: United States NHLBI

GRANT: P01 HL 076491

ACRONYM: HL

MEDLINETA: J Am Coll Cardiol

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