Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.
Protein Disulphide Isomerase and NADPH Oxidase 1 Cooperate to Control Platelet Function and Are Associated with Cardiometabolic Disease Risk Factors.
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蛋白质二硫化物异构酶和NADPH氧化酶1协同控制血小板功能并与心脏代谢疾病危险因素相关。
DOI：
10.3390/antiox10030497
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发表时间：
2021-03-23
期刊：
影响因子：
--
通讯作者：
Gibbins JM
中科院分区：
文献类型：
--
作者：
Gaspar RS;Sage T;Little G;Kriek N;Pula G;Gibbins JM
背景资料：蛋白质二硫化物异构酶（PDI）和NADPH氧化酶1（Nox-1）调节血小板功能和活性氧（ROS）的产生，表明潜在的相互依赖的作用。血小板反应性和ROS产生增加与心脏代谢疾病的危险因素相关。目的：探讨PDI与Nox-1是否协同调控血小板功能。方法：免疫荧光显微镜用于确定PDI和Nox-1的表达和定位。血小板聚集、纤维蛋白原结合、P-选择素暴露、扩散和钙动员被测量作为血小板功能的标志物。进行了一项横断面人群研究（n = 136），以评估血小板PDI和Nox-1水平与心脏代谢危险因素之间的关系。结果：PDI和Nox-1在胶原受体GPVI诱导的激活后共定位。PDI和Nox-1的共同抑制导致GPVI介导的血小板聚集、活化和钙通量的叠加抑制。这在用PDI抑制剂bepristat处理的小鼠Nox-1−/−血小板中得到证实，而不影响出血。PDI和Nox-1共同参与了涉及p38 MAPK、p47 phox、PKC和Akt磷酸化的GPVI信号传导。血小板PDI和Nox-1水平在肥胖中上调，血小板Nox-1在高血压个体中也升高。结论：我们发现PDI和Nox-1协同控制血小板功能，并与心脏代谢危险因素相关。
Background: Protein disulphide isomerase (PDI) and NADPH oxidase 1 (Nox-1) regulate platelet function and reactive oxygen species (ROS) generation, suggesting potentially interdependent roles. Increased platelet reactivity and ROS production have been correlated with cardiometabolic disease risk factors. Objectives: To establish whether PDI and Nox-1 cooperate to control platelet function. Methods: Immunofluorescence microscopy was utilised to determine expression and localisation of PDI and Nox-1. Platelet aggregation, fibrinogen binding, P-selectin exposure, spreading and calcium mobilization were measured as markers of platelet function. A cross-sectional population study (n = 136) was conducted to assess the relationship between platelet PDI and Nox-1 levels and cardiometabolic risk factors. Results: PDI and Nox-1 co-localized upon activation induced by the collagen receptor GPVI. Co-inhibition of PDI and Nox-1 led to additive inhibition of GPVI-mediated platelet aggregation, activation and calcium flux. This was confirmed in murine Nox-1−/− platelets treated with PDI inhibitor bepristat, without affecting bleeding. PDI and Nox-1 together contributed to GPVI signalling that involved the phosphorylation of p38 MAPK, p47phox, PKC and Akt. Platelet PDI and Nox-1 levels were upregulated in obesity, with platelet Nox-1 also elevated in hypertensive individuals. Conclusions: We show that PDI and Nox-1 cooperate to control platelet function and are associated with cardiometabolic risk factors.
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DOI：
10.1161/atvbaha.116.307461
发表时间：
2016-06
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Crescente M;Pluthero FG;Li L;Lo RW;Walsh TG;Schenk MP;Holbrook LM;Louriero S;Ali MS;Vaiyapuri S;Falet H;Jones IM;Poole AW;Kahr WH;Gibbins JM
通讯作者：
Gibbins JM
影响因子：
4
作者：
Gianni, Davide;Taulet, Nicolas;Zhang, Hui;DerMardirossian, Celine;Kister, Jeremy;Martinez, Luis;Roush, William R.;Brown, Steven J.;Bokoch, Gary M.;Rosen, Hugh
通讯作者：
Rosen, Hugh
DOI：
10.1161/atvbaha.116.307308
发表时间：
2016-05
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Delaney MK;Kim K;Estevez B;Xu Z;Stojanovic-Terpo A;Shen B;Ushio-Fukai M;Cho J;Du X
通讯作者：
Du X
影响因子：
--
作者：
Gaspar RS;Trostchansky A;Paes AM
通讯作者：
Paes AM
影响因子：
3.7
作者：
Chien, Chu-Yen;Hung, Yi-Jen;Lee, Chien-Hsing
通讯作者：
Lee, Chien-Hsing