title: Erythrocytes, leukocytes and platelets as a source of oxidative stress in chronic vascular diseases: detoxifying mechanisms and potential therapeutic options.
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 antioxidant molecules of plasma or cell origin can prevent ROS production. Free Hb binds to haptoglobin (Hp) and once Hp-Hb complex is endocytosed by CD163, liberated heme is converted into less toxic compounds by heme oxygenase-1. Iron homeostasis is mainly regulated by transferrin, 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, thioredoxin 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.
authors: Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain. jlmartin@fjd.es
authors: Jose Luis
authors: JL
authors: Martin-Ventura
authors: Julio
authors: J
authors: Madrigal-Matute
authors: Roxana
authors: R
authors: Martinez-Pinna
authors: Priscila
authors: P
authors: Ramos-Mozo
authors: Luis Miguel
authors: LM
authors: Blanco-Colio
authors: Juan Antonio
authors: JA
authors: Moreno
authors: Carlos
authors: C
authors: Tarin
authors: Elena
authors: E
authors: Burillo
authors: Carlos Ernesto
authors: CE
authors: Fernandez-Garcia
authors: Jesus
authors: J
authors: Egido
authors: Olivier
authors: O
authors: Meilhac
authors: Jean-Baptiste
authors: JB
authors: Michel
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D000975:Antioxidants / Q000627:therapeutic use; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000188:drug therapy; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy; D001792:Blood Platelets / Q000378:metabolism*; D002374:Catalase / Q000097:blood; D015913:Chelation Therapy; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000378:metabolism*; D006242:Haptoglobins / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood; D007962:Leukocytes / Q000378:metabolism*; D018384:Oxidative Stress; D009195:Peroxidase / Q000097:blood; D054464:Peroxiredoxins / Q000097:blood; D015539:Platelet Activation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood; D016897:Respiratory Burst; D013482:Superoxide Dismutase / Q000097:blood; D013879:Thioredoxins / Q000097:blood; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000975:Antioxidants; D000098902:CD163 Antigen; D006242:Haptoglobins; D017382:Reactive Oxygen Species; D011956:Receptors, Cell Surface; D006418:Heme; D013879:Thioredoxins; D007501:Iron; D054464:Peroxiredoxins; D002374:Catalase; D009195:Peroxidase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase