A new role for the A2b adenosine receptor in regulating platelet function

Yang, Dan; Chen, H.; Koupenova, Milka; Carroll, Shannon H.; Eliades, Alexia; Freedman, Jane E.; Toselli, Paul; Ravid, Katya

doi:10.1111/j.1538-7836.2010.03769.x

Cited by 89 publications

(87 citation statements)

References 37 publications

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“…Deletion of A 2B R increased catheter-induced intimal VSMC hyperplasia, together with increased TNF-␣ expression, effects probably mediated by bone marrow-derived platelets (2019); yet increased expression of adhesion molecules was seen on endothelium of whole body A 2B R KO mice (16). A 2B R activation increases cAMP, which is generally anti-inflammatory and also specifically downregulates expression P2Y 1 ADP receptors in platelets (2018).…”

Section: A Purinergic Signalingmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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Section: A Purinergic Signalingmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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“…The consequence of treatment with prostaglandin I 2 and PKA activity is overall platelet inhibition. The alpha2 type of adenosine receptors also suppress platelet aggregation by coupling to G s (325).…”

Section: Platelet Receptors For Soluble Agonistsmentioning

confidence: 99%

New Fundamentals in Hemostasis

Versteeg

Heemskerk

Levi

et al. 2013

Physiological Reviews

884

831

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Hemostasis encompasses the tightly regulated processes of blood clotting, platelet activation, and vascular repair. After wounding, the hemostatic system engages a plethora of vascular and extravascular receptors that act in concert with blood components to seal off the damage inflicted to the vasculature and the surrounding tissue. The first important component that contributes to hemostasis is the coagulation system, while the second important component starts with platelet activation, which not only contributes to the hemostatic plug, but also accelerates the coagulation system. Eventually, coagulation and platelet activation are switched off by blood-borne inhibitors and proteolytic feedback loops. This review summarizes new concepts of activation of proteases that regulate coagulation and anticoagulation, to give rise to transient thrombin generation and fibrin clot formation. It further speculates on the (patho)physiological roles of intra-and extravascular receptors that operate in response to these proteases. Furthermore, this review provides a new framework for understanding how signaling and adhesive interactions between endothelial cells, leukocytes, and platelets can regulate thrombus formation and modulate the coagulation process. Now that the key molecular players of coagulation and platelet activation have become clear, and their complex interactions with the vessel wall have been mapped out, we can also better speculate on the causes of thrombosis-related angiopathies.

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“…This may have implications in thrombosis, especially under conditions of injury or inflammation where A 2B receptor is upregulated in platelets. 25 Thus, consideration of the role of the P2Y 1 receptor in platelet aggregation and experimental thrombosis provides the rational for suggesting that this receptor could be a relevant target for new antiplatelet compounds.…”

Section: Platelet P2y 1 Receptormentioning

confidence: 99%

Purinergic Receptors in Thrombosis and Inflammation

Hechler

Gachet

2015

ATVB

142

101

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Abstract-Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y 1 , P2Y 12 , and P2X 1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y 2 , P2Y 6 , and P2X 7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.

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A new role for the A2b adenosine receptor in regulating platelet function

Cited by 89 publications

References 37 publications

Molecular Biology of Atherosclerosis

Molecular Biology of Atherosclerosis

New Fundamentals in Hemostasis

Purinergic Receptors in Thrombosis and Inflammation

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