Erythrocytes: Central Actors in Multiple Scenes of Atherosclerosis

Abstract

The development and progression of atherosclerosis (ATH) involves lipid accumulation, oxidative stress and both vascular and blood cell dysfunction. Erythrocytes, the main circulating cells in the body, exert determinant roles in the gas transport between tissues. Erythrocytes have long been considered as simple bystanders in cardiovascular diseases, including ATH. This review highlights recent knowledge concerning the role of erythrocytes being more than just passive gas carriers, as potent contributors to atherosclerotic plaque progression. Erythrocyte physiology and ATH pathology is first described. Then, a specific chapter delineates the numerous links between erythrocytes and atherogenesis. In particular, we discuss the impact of extravasated erythrocytes in plaque iron homeostasis with potential pathological consequences. Hyperglycaemia is recognised as a significant aggravating contributor to the development of ATH. Then, a special focus is made on glycoxidative modifications of erythrocytes and their role in ATH. This chapter includes recent data proposing glycoxidised erythrocytes as putative contributors to enhanced atherothrombosis in diabetic patients.

Eryptosis: Programmed Death of Nucleus-Free, Iron-Filled Blood Cells

“…Erythrocytes are the main cellular constituents of human blood, and the involvement of erythrocytes in the manifestation of atherosclerotic plaque formation has been discussed [89]. Furthermore, several diseases with anemic complications have been associated with enhanced eryptosis.…”

Olive Oil Phenols Prevent Mercury-Induced Phosphatidylserine Exposure and Morphological Changes in Human Erythrocytes Regardless of Their Different Scavenging Activity

“…As a matter of fact, PS translocation to the cell surface represents a key hallmark of erythrocyte programmed cell death, also called eryptosis [ 16 , 17 , 18 , 19 ]. Similarly to apoptosis of nucleated cells, RBC can enter a programmed suicidal death that allows cell degradation without producing toxic by-products, preventing the release of harmful cellular components such as hemoglobin, heme and free iron that can favor plaque formation [ 20 ]. This specific membrane alteration, however, can lead to adverse effects on the cardiovascular system, by providing a binding site for prothrombinase complex as well as by inducing unusual adhesion between RBC with both endothelial cells and other cells in the bloodstream, thus resulting in clot formation and microvascular occlusion [ 21 , 22 , 23 ].…”

Impact of Enhanced Phagocytosis of Glycated Erythrocytes on Human Endothelial Cell Functions

“…Endothelium barrier and microvessel disruption may bring large amounts of erythrocytes into the plaque, participating in its progression and complication [ 11 ]. Then, extravasated erythrocytes, as a source of cholesterol, hemoglobin and iron, can generate a deleterious environment contributing to oxidative stress and plaque rupture [ 11 , 12 , 13 ].…”

“…Oxidative stress (OS) and damage can also occur in the vascular compartment and imply impaired/oxidized erythrocytes as central stressors in the promotion of diabetic complications [ 3 , 12 , 14 ]. In hyperglycemic conditions, erythrocytes are subject to glycation.…”