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The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players

Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play a key role in the atherothrombotic process through the release of inflammatory mediators and formation of thrombi. In healthy blood vessels, excessive pla...

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Autores principales: Raslan, Zaher, Aburima, Ahmed, Naseem, Khalid M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639615/
https://www.ncbi.nlm.nih.gov/pubmed/26617518
http://dx.doi.org/10.3389/fphar.2015.00266
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author Raslan, Zaher
Aburima, Ahmed
Naseem, Khalid M.
author_facet Raslan, Zaher
Aburima, Ahmed
Naseem, Khalid M.
author_sort Raslan, Zaher
collection PubMed
description Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play a key role in the atherothrombotic process through the release of inflammatory mediators and formation of thrombi. In healthy blood vessels, excessive platelet activation is restricted by endothelial-derived prostacyclin (PGI(2)) through cyclic adenosine-5′-monophosphate (cAMP) and protein kinase A (PKA)-dependent mechanisms. Elevation in intracellular cAMP is associated with the control of a number of distinct platelet functions including actin polymerisation, granule secretion, calcium mobilization and integrin activation. Unfortunately, in atherosclerotic disease the protective effects of cAMP are compromised, which may contribute to pathological thrombosis. The cAMP signaling network in platelets is highly complex with the presence of multiple isoforms of adenylyl cyclase (AC), PKA, and phosphodiesterases (PDEs). However, a precise understanding of the relationship between specific AC, PKA, and PDE isoforms, and how individual signaling substrates are targeted to control distinct platelet functions is still lacking. In other cells types, compartmentalisation of cAMP signaling has emerged as a key mechanism to allow precise control of specific cell functions. A-kinase anchoring proteins (AKAPs) play an important role in this spatiotemporal regulation of cAMP signaling networks. Evidence of AKAP-mediated compartmentalisation of cAMP signaling in blood platelets has begun to emerge and is providing new insights into the regulation of platelet function. Dissecting the mechanisms that allow cAMP to control excessive platelet activity without preventing effective haemostasis may unleash the possibility of therapeutic targeting of the pathway to control unwanted platelet activity.
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spelling pubmed-46396152015-11-27 The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players Raslan, Zaher Aburima, Ahmed Naseem, Khalid M. Front Pharmacol Pharmacology Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play a key role in the atherothrombotic process through the release of inflammatory mediators and formation of thrombi. In healthy blood vessels, excessive platelet activation is restricted by endothelial-derived prostacyclin (PGI(2)) through cyclic adenosine-5′-monophosphate (cAMP) and protein kinase A (PKA)-dependent mechanisms. Elevation in intracellular cAMP is associated with the control of a number of distinct platelet functions including actin polymerisation, granule secretion, calcium mobilization and integrin activation. Unfortunately, in atherosclerotic disease the protective effects of cAMP are compromised, which may contribute to pathological thrombosis. The cAMP signaling network in platelets is highly complex with the presence of multiple isoforms of adenylyl cyclase (AC), PKA, and phosphodiesterases (PDEs). However, a precise understanding of the relationship between specific AC, PKA, and PDE isoforms, and how individual signaling substrates are targeted to control distinct platelet functions is still lacking. In other cells types, compartmentalisation of cAMP signaling has emerged as a key mechanism to allow precise control of specific cell functions. A-kinase anchoring proteins (AKAPs) play an important role in this spatiotemporal regulation of cAMP signaling networks. Evidence of AKAP-mediated compartmentalisation of cAMP signaling in blood platelets has begun to emerge and is providing new insights into the regulation of platelet function. Dissecting the mechanisms that allow cAMP to control excessive platelet activity without preventing effective haemostasis may unleash the possibility of therapeutic targeting of the pathway to control unwanted platelet activity. Frontiers Media S.A. 2015-11-10 /pmc/articles/PMC4639615/ /pubmed/26617518 http://dx.doi.org/10.3389/fphar.2015.00266 Text en Copyright © 2015 Raslan, Aburima and Naseem. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Raslan, Zaher
Aburima, Ahmed
Naseem, Khalid M.
The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title_full The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title_fullStr The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title_full_unstemmed The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title_short The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players
title_sort spatiotemporal regulation of camp signaling in blood platelets—old friends and new players
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639615/
https://www.ncbi.nlm.nih.gov/pubmed/26617518
http://dx.doi.org/10.3389/fphar.2015.00266
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