Erythrocytes, leukocytes and platelets as a source of oxidative stress in chronic vascular diseases: Detoxifying mechanisms and potential therapeutic options

Jose Luis Martin-Ventura, Julio Madrigal-Matute, Roxana Martinez-Pinna, Priscila Ramos-Mozo, Luis Miguel Blanco-Colio, Juan Antonio Moreno, Carlos Tarin, Elena Burillo, Carlos Ernesto Fernandez-Garcia, Jesus Egido, Olivier Meilhac, Jean Baptiste Michel

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48 Scopus citations

Abstract

Oxidative stress is involved in the chronic pathological vascular remodelling of both abdominal aortic aneurysm and occlusive atherosclerosis. Red blood cells (RBCs), leukocytes and platelets present in both, aneurysmal intraluminal thrombus and intraplaque haemorraghes, could be involved in the redox imbalance inside diseased arterial tissues. RBCs haemolysis may release the pro-oxidant haemoglobin (Hb), which transfers heme to tissue and low-density lipoproteins. Heme-iron potentiates molecular, cell and tissue toxicity mediated by leukocytes and other sources of reactive oxygen species (ROS). Polymorphonuclear neutrophils release myeloperoxidase and, along with activated platelets, produce superoxide mediated by NADPH oxidase, causing oxidative damage. In response to this pro-oxidant milieu, several anti-oxidant molecules of plasma or cell origin can prevent ROS production. Free Hb binds to haptoglobin (Hp) and once Hp-Hb complex is endocy-tosed by CD163, liberated heme is converted into less toxic compounds by heme oxygenase-1. Iron homeostasis is mainly regulated by transfer-rin, which transports ferric ions to other cells. Transferrin-bound iron is internalised via endocytosis mediated by transferrin receptor. Once inside the cell, iron is mainly stored by ferritin. Other non hemo-iron related antioxidant enzymes (e.g. superoxide dismutase, catalase, thio-redoxin and peroxiredoxin) are also involved in redox modulation in vascular remodelling. Oxidative stress is a main determinant of chronic pathological remodelling of the arterial wall, partially linked to the presence of RBCs, leukocytes, platelets and oxidised fibrin within tissue and to the imbalance between pro-/anti-oxidant molecules. Understanding the complex mechanisms underlying redox imbalance could help to define novel potential targets to decrease atherothrombotic risk.

Original languageEnglish (US)
Pages (from-to)435-442
Number of pages8
JournalThrombosis and Haemostasis
Volume108
Issue number3
DOIs
Publication statusPublished - Sep 1 2012

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Keywords

  • Antioxidants
  • Atherosclerosis
  • Oxidative stress
  • Vascular remodelling

ASJC Scopus subject areas

  • Hematology

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