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

doi:10.1160/TH12-04-0248

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2012; 108(03): 435-442
DOI: 10.1160/TH12-04-0248

Theme Issue Article

Schattauer GmbH

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

Jose Luis Martin-Ventura

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Julio Madrigal-Matute

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Roxana Martinez-Pinna

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Priscila Ramos-Mozo

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Luis Miguel Blanco-Colio

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Juan Antonio Moreno

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Carlos Tarin

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Elena Burillo

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Carlos Ernesto Fernandez-Garcia

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Jesus Egido

¹Vascular Research Lab, IIS-Fundación Jiménez Diaz-Autonoma University, Madrid, Spain

,

Olivier Meilhac

²Inserm, U698, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris, France

,

Jean-Baptiste Michel

²Inserm, U698, Université Paris Diderot, Sorbonne Paris Cité, AP-HP, Hôpital Bichat, Paris, France

› Institutsangaben

Abstract

Summary

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 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.

Keywords

Oxidative stress - atherosclerosis - vascular remodelling - antioxidants

Volltext

Referenzen

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