Red Blood Cell Function and Dysfunction: Redox Regulation, Nitric Oxide Metabolism, Anemia

Abstract

Significance: Recent clinical evidence identified anemia to be correlated with severe complications of cardiovascular disease (CVD) such as bleeding, thromboembolic events, stroke, hypertension, arrhythmias, and inflammation, particularly in elderly patients. The underlying mechanisms of these complications are largely unidentified.Recent Advances: Previously, red blood cells (RBCs) were considered exclusively as transporters of oxygen and nutrients to the tissues. More recent experimental evidence indicates that RBCs are important interorgan communication systems with additional functions, including participation in control of systemic nitric oxide metabolism, redox regulation, blood rheology, and viscosity. In this article, we aim to revise and discuss the potential impact of these noncanonical functions of RBCs and their dysfunction in the cardiovascular system and in anemia.Critical Issues: The mechanistic links between changes of RBC functional properties and cardiovascular complications related to anemia have not been untangled so far.Future Directions: To allow a better understanding of the complications associated with anemia in CVD, basic and translational science studies should be focused on identifying the role of noncanonical functions of RBCs in the cardiovascular system and on defining intrinsic and/or systemic dysfunction of RBCs in anemia and its relationship to CVD both in animal models and clinical settings. Antioxid. Redox Signal. 26, 718–742.

Association Between Changes in Hemoglobin Concentration and Cardiovascular Risks and All‐Cause Mortality Among Young Women

“…If red blood cells, which play an important role in transporting oxygen from the lungs to other organs, are decreased, vascular resistance will be systemically reduced and affect cardiocerebrovascular systems 25. Under conditions of chronic anemia, compensation of reduced perfusion leads to increased cardiac output by increasing the preload and decreasing the afterload, thereby inducing left ventricular hypertrophy 26.…”

“…Under conditions of chronic anemia, compensation of reduced perfusion leads to increased cardiac output by increasing the preload and decreasing the afterload, thereby inducing left ventricular hypertrophy 26. Moreover, decreased hematocrit leads to changes in red blood cell–mediated nitric oxide metabolism, increasing cardiac output 25. Another proposal is that decreased hematocrit activates erythrocyte‐derived adenosine diphosphate, which stimulates platelet activation and increases platelet adhesiveness, thereby elevating the risk of atherosclerosis and thrombosis,27, 28 which can cause ischemic cardiocerebrovascular diseases.…”

Assessment of iron status and interplay between lipid peroxidation and antioxidant capacity in common hemoglobin variants in Osun State, southwestern Nigeria

“…Hemoglobin (Hb) and iron released from erythrocytes in biological systems are associated with uninterrupted prooxidant generation attributed to superoxide anion via autoxidation of Hb and Fenton's reaction . Iron is a key element that sometimes prompts Hb oxidation . Increased free iron in Hb variants is linked with increase in reactive free radicals that may in turn set off oxidative stress .…”

“…This is in opposite to the ample available data on SCD, although without resolute agreement at present. More so, there are still conflicting reports on the rate of activities of various antioxidant enzymes such as SOD, CAT, and GPx in SCDs . We therefore aimed to assess the interplay between erythrocyte lipid peroxidation and antioxidant defense system in all common Hb variants—both SCDs and the carriers in relation to possible links to iron mediation.…”

Paracetamol and Hydrogen peroxide-induced tissue alterations are reduced by Costus afer extract

“…In the presence of transition metals (which are redox active), the erythrocytes are vulnerable to oxidative attack and, thus, have been used to study the effects of reactive oxygen species/antioxidants [25,26]. Hydrogen peroxide on the other hand is a potent reactive oxygen species that degrades heme, which leads to the release of redox active Fe ions that can initiate free radical production [27].…”