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 M. Wiley, Annapoorna Kini, Samin K. Sharma, Valentin Fuster, Pedro R. Moreno

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Haptoglobins
Atherosclerosis
Hemoglobins
Genotype
Hemorrhage
Heme Oxygenase-1
Vascular Cell Adhesion Molecule-1
Interleukin-10
Peroxidase
Smooth Muscle
Actins
Proteins
Iron
Macrophages
Atherectomy
Genes
Atherosclerotic Plaques
Diabetes Mellitus
Carrier Proteins
Anti-Inflammatory Agents

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis. / Purushothaman, Meerarani; Krishnan, Prakash; Purushothaman, K. Raman; Baber, Usman; Tarricone, Arthur; Perez, Juan S.; Wiley, Jose M.; Kini, Annapoorna; Sharma, Samin K.; Fuster, Valentin; Moreno, Pedro R.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 32, No. 11, 11.2012, p. 2769-2775.

Research output: Contribution to journalArticle

Purushothaman, M, Krishnan, P, Purushothaman, KR, Baber, U, Tarricone, A, Perez, JS, Wiley, JM, Kini, A, Sharma, SK, Fuster, V & Moreno, PR 2012, 'Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 11, pp. 2769-2775. https://doi.org/10.1161/ATVBAHA.112.252122
Purushothaman, Meerarani ; Krishnan, Prakash ; Purushothaman, K. Raman ; Baber, Usman ; Tarricone, Arthur ; Perez, Juan S. ; Wiley, Jose M. ; Kini, Annapoorna ; Sharma, Samin K. ; Fuster, Valentin ; Moreno, Pedro R. / Genotype-dependent impairment of hemoglobin clearance increases oxidative and inflammatory response in human diabetic atherosclerosis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2012 ; Vol. 32, No. 11. pp. 2769-2775.
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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.",
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AU - Purushothaman, Meerarani

AU - Krishnan, Prakash

AU - Purushothaman, K. Raman

AU - Baber, Usman

AU - Tarricone, Arthur

AU - Perez, Juan S.

AU - Wiley, Jose M.

AU - Kini, Annapoorna

AU - Sharma, Samin K.

AU - Fuster, Valentin

AU - Moreno, Pedro R.

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AB - 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.

KW - Atherosclerosis

KW - Diabetes mellitus

KW - Haptoglobin

KW - Inflammation

KW - Oxidative stress

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