Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells.
Surface expression of collagen receptor Fc receptor-gamma/glycoprotein VI is enhanced on platelets in type 2 diabetes and mediates release of CD40 ligand and activation of endothelial cells.
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2 型糖尿病患者血小板上胶原蛋白受体 Fc 受体-γ/糖蛋白 VI 的表面表达增强，并介导 CD40 配体的释放和内皮细胞的激活。
作者：
N. Cabeza;Zhongyan Li;C. Schulz;E. Kremmer;S. Massberg;A. Bültmann;M. Gawaz
糖尿病与胶原蛋白介导的血小板活化增强有关，这对血栓缺血并发症有显着影响。在这项研究中，对 385 名 2 型糖尿病患者的血小板胶原受体糖蛋白 VI (GPVI) 进行了研究。与非糖尿病患者相比，糖尿病患者中与 GPVI 形成功能复合物的血小板 Fc 受体的表面表达显着增加（P = 0.02）。 Fc 受体表达与 GPVI 表达相关，并被发现与糖尿病独立相关（r = 0.529，P < 0.001）。通过特异性抗 GPVI 单克隆抗体刺激 GPVI 显着增强 CD40L 的表面表达 (P = 0.006)。由于 CD40L 是一种有效的血小板衍生细胞因子，参与血栓形成和动脉粥样硬化，因此我们评估了 GPVI 介导的 CD40L 释放对内皮细胞活化的影响。 GPVI刺激的血小板共孵育导致CD62P、αvβ3和细胞间粘附分子1的内皮表面表达显着增强（P < 0.05）以及培养的人脐静脉内皮细胞的单核细胞趋化蛋白1的分泌（P < 0.01）。这些结果表明胶原蛋白受体 GPVI 的功能在 2 型糖尿病中发生改变，并且可能在动脉粥样硬化血栓并发症中发挥重要作用。抑制 GPVI 可能是治疗高危糖尿病患者的一个有前途的药理学靶点。
Diabetes is associated with an enhanced collagen-mediated platelet activation that contributes significantly to thromboischemic complications. In this study, the platelet collagen receptor glycoprotein VI (GPVI) was studied in 385 patients with type 2 diabetes. Surface expression of the platelet Fc receptor that forms a functional complex with GPVI was significantly increased in patients with diabetes compared with those without diabetes (P = 0.02). Fc receptor expression correlated with GPVI expression and was found to be independently associated with diabetes (r = 0.529, P < 0.001). Stimulation of GPVI through a specific anti-GPVI monoclonal antibody significantly enhanced surface expression of CD40L (P = 0.006). Because CD40L is a potent platelet-derived cytokine that is involved in thrombosis and atherosclerosis, we evaluated the effect of GPVI-mediated release of CD40L on activation of endothelial cells. Coincubation of GPVI-stimulated platelets resulted in substantial enhanced endothelial surface expression of CD62P, alphavbeta3, and intercellular adhesion molecule 1 (P < 0.05) and secretion of monocyte chemoattractant protein 1 of cultured human umbilical vein endothelial cells (P < 0.01). These results suggest that the function of collagen receptor GPVI is altered in type 2 diabetes and may play an important role in atherothrombotic complications. Inhibition of GPVI may be a promising pharmacological target in the treatment of high-risk diabetic patients.
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DOI：
10.1073/pnas.97.13.7458
发表时间：
2000-06-20
影响因子：
11.1
作者：
Schönbeck, U;Sukhova, GK;Libby, P
通讯作者：
Libby, P
糖尿病中血小板血栓素合成增加。
DOI：
--
发表时间：
1981
期刊：
The Journal of laboratory and clinical medicine
影响因子：
--
作者：
Halushka,PV;Rogers,RC;Loadholt,CB;Colwell,JA
通讯作者：
Colwell,JA
内皮细胞死亡后，血小板积聚在糖尿病视网膜血管系统中，并抑制血-视网膜屏障的破坏。
DOI：
10.1016/s0002-9440(10)63648-6
发表时间：
2003
期刊：
The American journal of pathology
影响因子：
--
作者：
Yamashiro,Kenji;Tsujikawa,Akitaka;Ishida,Susumu;Usui,Tomohiko;Kaji,Yuichi;Honda,Yoshihito;Ogura,Yuichiro;Adamis,AnthonyP
通讯作者：
Adamis,AnthonyP
DOI：
10.1016/s0735-1097(01)01555-8
发表时间：
2001-11-01
影响因子：
24
作者：
Osende, JI;Badimon, JJ;Crandall, JP
通讯作者：
Crandall, JP