Neovascularization and intra-plaque hemorrhage: Role of haptoglobin, macrophages, and heme-oxygenase-1 pathway

K. Raman Purushothaman, Meerarani Purushothaman, Andrew P. Levy, Samin K. Sharma, Valentin Fuster, Pedro R. Moreno

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

1 Scopus citations


Advanced atherosclerosis is characterized by increased revascularization, intraplaque hemorrhage, macrophage activation and iron deposition. The dysfunctional fragile neovessels may rupture, leading to intra-plaque hemorrhage with the subsequent release of hemoglobin from extravasated erythrocytes. Free hemoglobin is a potent inducer of oxidative stress and exerts toxic effects through macrophage activation and inflammatory stimulus. The defense mechanism to antagonize these deleterious effects of hemoglobin is mediated by haptoglobin. The hemoglobin binds to haptoglobin to form Hemoglobin-Haptoglobin complex and the clearance of this complex is mediated by the macrophage scavenger receptor CD163. Inside the macrophage, the free heme released from hemoglobin is metabolized by Heme Oxygenase-1 attenuating heme toxicity. Pathobiological mechanisms associated in this pathway and the risk-factor modulation induced by diabetes mellitus are revised in this chapter, highlighting its pivotal role in the atherosclerotic disease progression and plaque vulnerability.

Original languageEnglish
Title of host publicationTherapeutic Angiogenesis for Vascular Diseases
Subtitle of host publicationMolecular Mechanisms and Targeted Clinical Approaches for the Treatment of Angiogenic Disease
PublisherSpringer Netherlands
Number of pages20
ISBN (Print)9789048194940
StatePublished - 2011


  • Diabetes mellitus
  • Haptoglobin genotype
  • Hemeoxygenase-1
  • Intraplaque hemorrhage
  • Macrophage scavenger receptor CD163


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