Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.
Platelet Transcriptome Profiling in HIV and ATP-Binding Cassette Subfamily C Member 4 (ABCC4) as a Mediator of Platelet Activity.
复制标题
DOI：
10.1016/j.jacbts.2017.10.005
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Berger JS
中科院分区：
文献类型：
--
作者：
Marcantoni E;Allen N;Cambria MR;Dann R;Cammer M;Lhakhang T;O'Brien MP;Kim B;Worgall T;Heguy A;Tsirigos A;Berger JS
在接受抗逆转录病毒治疗的病毒学抑制HIV患者中，血小板活性及其效应细胞特性增加。与健康个体相比，HIV参与者的血小板转录组表达差异。与健康个体相比，HIV感染者中ABCC 4的表达和翻译增强。ABCC 4是一种膜转运蛋白，在调节包括血小板活化和聚集在内的多种心血管过程中发挥重要作用。HIV中的血小板ABCC 4抑制通过调节环核苷酸稳态和血小板促炎介质的排出来减弱血小板活化和血小板效应细胞功能。一个公正的血小板转录谱确定ATP结合盒亚家族C成员4（ABCC 4）作为一种新的调解人的血小板活性在病毒学抑制的人类免疫缺陷病毒（HIV）感染的受试者抗逆转录病毒治疗。使用离体和体外细胞和分子测定，我们证明了ABCC 4通过cAMP-蛋白激酶A（PKA）介导的机制改变颗粒释放和环核苷酸稳态来调节血小板活化。血小板ABCC 4抑制通过减少炎性介质如鞘氨醇-1-磷酸的释放来减弱血小板活化和效应细胞功能。ABCC 4抑制可能是一种新的抗血栓策略，在HIV感染的受试者抗逆转录病毒治疗。
Platelet activity and its effector cell properties are increased in persons with virologically suppressed HIV on antiretroviral therapy. The platelet transcriptome is differentially expressed in participants with HIV compared with healthy individuals. ABCC4 expression and translation was enhanced in HIV-infected subjects compared with healthy individuals. ABCC4 is a membrane transporter that plays an important role in regulating several cardiovascular processes, including platelet activation and aggregation. Platelet ABCC4 inhibition in HIV attenuated platelet activation and platelet effector cell function by regulating cyclic nucleotide homeostasis and the extrusion of platelet proinflammatory mediators. An unbiased platelet transcriptome profile identified ATP binding cassette subfamily C member 4 (ABCC4) as a novel mediator of platelet activity in virologically suppressed human immunodeficiency virus (HIV)-infected subjects on antiretroviral therapy. Using ex vivo and in vitro cellular and molecular assays we demonstrated that ABCC4 regulated platelet activation by altering granule release and cyclic nucleotide homeostasis through a cAMP-protein kinase A (PKA)–mediated mechanism. Platelet ABCC4 inhibition attenuated platelet activation and effector cell function by reducing the release of inflammatory mediators, such as sphingosine-1-phosphate. ABCC4 inhibition may represent a novel antithrombotic strategy in HIV-infected subjects on antiretroviral therapy.
登录
查看更多内容
影响因子：
39
作者：
Freiberg MS;Chang CC;Kuller LH;Skanderson M;Lowy E;Kraemer KL;Butt AA;Bidwell Goetz M;Leaf D;Oursler KA;Rimland D;Rodriguez Barradas M;Brown S;Gibert C;McGinnis K;Crothers K;Sico J;Crane H;Warner A;Gottlieb S;Gottdiener J;Tracy RP;Budoff M;Watson C;Armah KA;Doebler D;Bryant K;Justice AC
通讯作者：
Justice AC
影响因子：
5.8
作者：
Cheung, Leanna;Flemming, Claudia L.;Norris, Murray D.
通讯作者：
Norris, Murray D.
影响因子：
6.7
作者：
Borgognone, Alessandra;Pulcinelli, Fabio Maria
通讯作者：
Pulcinelli, Fabio Maria
影响因子：
64.5
作者：
Denis, MM;Tolley, ND;Weyrich, AS
通讯作者：
Weyrich, AS
DOI：
10.1097/hjr.0b013e328336a150
发表时间：
2010-10-01
影响因子：
--
作者：
Friis-Moller, Nina;Thiebaut, Rodolphe;Law, Matthew G.
通讯作者：
Law, Matthew G.