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Neovascularization and Intra-plaque Hemorrhage: Role of Haptoglobin, Macrophages, and Heme-Oxygenase-1 Pathway

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Therapeutic Angiogenesis for Vascular Diseases

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Abstract

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.

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Authors and Affiliations

  1. From the Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY, USA

    K-Raman Purushothaman, Meerarani Purushothaman, Andrew P. Levy, Samin K. Sharma & Valentin Fuster

  2. Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1030, New York, 10029, NY, USA

    Pedro R. Moreno (Associate Professor of Medicine)

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  1. K-Raman Purushothaman
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  2. Meerarani Purushothaman
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  3. Andrew P. Levy
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  4. Samin K. Sharma
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  5. Valentin Fuster
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  6. Pedro R. Moreno
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Correspondence to Pedro R. Moreno .

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    Mark Slevin

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Purushothaman, KR., Purushothaman, M., Levy, A.P., Sharma, S.K., Fuster, V., Moreno, P.R. (2010). Neovascularization and Intra-plaque Hemorrhage: Role of Haptoglobin, Macrophages, and Heme-Oxygenase-1 Pathway. In: Slevin, M. (eds) Therapeutic Angiogenesis for Vascular Diseases. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9495-7_10

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