Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis

Meerarani Purushothaman, Prakash Krishnan, K. Raman Purushothaman, Usman Baber, Arthur Tarricone, Juan S. Perez, Jose Wiley, Annapoorna Kini, Samin K. Sharma, Valentin Fuster, Pedro R. Moreno

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective-Haptoglobin (Hp) protein is responsible for hemoglobin clearance after intra-plaque hemorrhage. Hp gene exists as Hp-1 and Hp-2 alleles and the phenotypes show important molecular heterogeneity. We tested the hypothesis that hemoglobin clearance may be deficient in diabetic atheroma from patients with Hp2-2, triggering increased oxidative, inflammatory, and angiogenic patterns compared with controls. Methods and Results-Forty patients with diabetes mellitus were genotyped and their peripheral plaques compared after atherectomy. Plaque hemorrhage, iron content, hemoglobin-binding protein CD163, and heme-oxygenase-1 were quantified. Oxidative, inflammatory, and angiogenic patterns were evaluated by measuring myeloperoxidase, interleukin-10, macrophages, vascular cell adhesion molecule-1, smooth muscle actin, and plaque neovascularization (CD34/CD31). Plaques with Hp2-2 (n=7) had increased hemorrhage (P<0.005), iron content (P<0.001), and reduced CD163 expression (P<0.002) compared with controls (n=14). Hp2-2 plaques had increased heme-oxygenase-1 protein (P<0.02), myeloperoxidase gene (P<0.05), and protein (P<0.0001). Anti-inflammatory interleukin-10 gene (P<0.04), and protein expressions (P<0.0001) were decreased in Hp2-2. Finally, macrophage (P<0.0001), vascular cell adhesion molecule-1 (P=0.001), smooth muscle actin (P=0.002) scores, and neovessels density (P<0.0001) were increased in Hp2-2. Conclusion-Genotype-dependent impairment of hemoglobin clearance after intra-plaque hemorrhage is associated with increased oxidative, inflammatory, and angiogenic response in human diabetic atherosclerosis.

Original languageEnglish (US)
Pages (from-to)2769-2775
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • Atherosclerosis
  • Diabetes mellitus
  • Haptoglobin
  • Inflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Purushothaman, M., Krishnan, P., Purushothaman, K. R., Baber, U., Tarricone, A., Perez, J. S., Wiley, J., Kini, A., Sharma, S. K., Fuster, V., & Moreno, P. R. (2012). Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology, 32(11), 2769-2775. https://doi.org/10.1161/ATVBAHA.112.252122