Purinergic interplay between erythrocytes and platelets in diabetes-associated vascular dysfunction

Abstract

Cardiovascular complications in diabetes are the leading causes for high morbidity and mortality. It has been shown that alteration of purinergic signaling contributes to diabetes-associated cardiovascular complications. Red blood cells (RBCs) and platelets play a fundamental role in regulation of oxygen transport and hemostasis, respectively. Of note, these cells undergo purinergic dysfunction in diabetes. Recent studies have established a novel function of RBCs as disease mediators for the development of endothelial dysfunction in type 2 diabetes (T2D). RBC-released ATP is defective in T2D, which has implication for induction of vascular dysfunction by dysregulating purinergic signaling. Platelets are hyperactive in diabetes. ADP-mediated P2Y1 and P2Y12 receptor activation contributes to platelet aggregation and targeting P2Y receptors particularly P2Y12 receptor in platelets is effective for the treatment of cardiovascular events. In contrast to other P2Y12 receptor antagonists, platelet-targeting drug ticagrelor has potential to initiate purinergic signaling in RBCs for the beneficial cardiovascular outcomes. It is increasingly clear that altered vascular purinergic signaling mediated by various nucleotides and nucleoside contributes to diabetes-associated vascular dysfunction. However, the contribution of complex purinergic networks between RBCs and platelets to the vascular dysfunction in diabetes remains unclear. This study discusses the possible interplay of RBCs and platelets via the purinergic network for diabetes-associated vascular dysfunction.

Erythrocytes from patients with ST-elevation myocardial infarction induce cardioprotection through the purinergic P2Y13 receptor and nitric oxide signaling

“…We therefore investigated whether ATP may be involved in the cardioprotective effect of RBCs from STEMI patients. Purinergic signaling involves the activation of membrane-bound P1 and P2 receptors by extracellular nucleosides and nucleotides including adenosine and ATP, respectively [ 37 , 47 ]. Previous observations suggest that P2 receptors including cardiomyocyte P2Y 2 and P2Y 11 receptors mediate cardioprotection [ 2 , 21 ].…”

Erythrocytes as Messengers for Information and Energy Exchange between Cells

“…The P2Y13 receptor is activated by ADP on erythrocytes leading to diminishing of ATP export. Purinergic signaling in erythrocytes is part of the interaction between erythrocytes, platelets, and endothelial cells, both in normal physiological conditions and in pathological conditions such as diabetes [101].…”

“…Heme and ATP can be generated from erythrocytes as a consequence of hemolysis. The intracellular pool of adenosine can be replenished by equilibrative nucleoside transporter 1 [101], which is a transporter localized in the plasma membrane of erythrocytes and other Erythrocytes as Messengers for Information and Energy Exchange between Cells DOI: http://dx.doi.org/10.5772/intechopen.108321 cells. AMP can then be regenerated in the erythrocyte from adenosine by adenosine kinase [107], an enzyme in the purine nucleotide salvage pathway [108].…”