Resolvin E1 regulates adenosine diphosphate activation of human platelets.

Content Provider	Semantic Scholar
Author	Fredman, Gabrielle Dyke, Thomas E. Van Serhan, Charles Nicholas
Copyright Year	2010
Abstract	OBJECTIVE To investigate the ability of resolvin E1 (RvE1) to regulate adenosine diphosphate (ADP) activation of platelets via specific receptors because RvE1 reduces platelet aggregation with certain agonists, including ADP. METHODS AND RESULTS RvE1 is an eicosapentaenoic acid-derived specialized proresolving mediator generated during the resolution of acute inflammation. RvE1 exhibits potent organ-protective actions in vivo and acts on specific cell types, including platelets. RvE1, 0.1 to 100 nmol/L, incubated with platelets gave reduced ADP-stimulated P-selectin mobilization (IC(50), approximately 1.6×10(-12) mol/L) and polymerized actin content compared with control platelets. RvE1, 1 to 100 nmol/L, did not stimulate or block intracellular Ca(2+) mobilization. By using a new P2Y(12)-β-arrestin-coupled cell system, ADP-activated P2Y(12) with an EC(50) of 5×10(-6) mol/L and RvE1 did not directly stimulate P2Y(12) or block the ADP-P2Y(12) signals. In this system, another eicosanoid, leukotriene E(4) (LTE(4)) (EC(50), 1.3×10(-11) mol/L), dose dependently activated P2Y(12). When recombinant P2Y(12)-expressing cells were transiently transfected with an RvE1 receptor, human ChemR23 (present on human platelets), with the addition of RvE1 (0.1-10.0 nmol/L), blocked ADP signals (IC(50), approximately 1.6×10(-11) mol/L) in P2Y(12)-ChemR23-expressing cells compared with mock transfections. CONCLUSIONS RvE1's regulatory actions (ie, reducing ADP-stimulated P-selectin mobilization and actin polymerization) are human (h)ChemR23-dependent. Moreover, specific platelet actions of RvE1 selectively engaged with ADP-activated platelets that illuminate a new cellular mechanism and affect ω-3 eicosapentaenoic acid, which may contribute to both resolution of vascular inflammation and ADP-dependent platelet activation relevant in pathological cardiovascular events.
Starting Page	154
Ending Page	158
Page Count	5
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://atvb.ahajournals.org/content/atvbaha/30/10/2005.full.pdf?download=true
PubMed reference number	20702811v1
Alternate Webpage(s)	https://doi.org/10.1161/ATVBAHA.110.209908
DOI	10.1161/atvbaha.110.209908
Journal	Arteriosclerosis, thrombosis, and vascular biology
Volume Number	30
Issue Number	10
Language	English
Access Restriction	Open
Subject Keyword	Adenosine Diphosphate Alprostadil Arachidonate 5-Lipoxygenase Blood Platelets CMKLR1 wt Allele Calcium DUOXA1 gene Eicosanoids Eicosapentaenoic Acid Exhibits as Topic F-Actin Inflammation Leukotrienes Mediator brand of benfluorex hydrochloride P-Selectin Recombinants Resolvin Selectins Thioctic Acid Transfection Vascular Diseases actin filament polymerization cell type incubated
Content Type	Text
Resource Type	Article