TY - JOUR
T1 - Erythrocytes, leukocytes and platelets as a source of oxidative stress in chronic vascular diseases
T2 - Detoxifying mechanisms and potential therapeutic options
AU - Martin-Ventura, Jose Luis
AU - Madrigal-Matute, Julio
AU - Martinez-Pinna, Roxana
AU - Ramos-Mozo, Priscila
AU - Blanco-Colio, Luis Miguel
AU - Moreno, Juan Antonio
AU - Tarin, Carlos
AU - Burillo, Elena
AU - Fernandez-Garcia, Carlos Ernesto
AU - Egido, Jesus
AU - Meilhac, Olivier
AU - Michel, Jean Baptiste
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Atherosclerosis
KW - Oxidative stress
KW - Vascular remodelling
UR - http://www.scopus.com/inward/record.url?scp=84865818831&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84865818831&partnerID=8YFLogxK
U2 - 10.1160/TH12-04-0248
DO - 10.1160/TH12-04-0248
M3 - Article
C2 - 22836558
AN - SCOPUS:84865818831
SN - 0340-6245
VL - 108
SP - 435
EP - 442
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 3
ER -