Decreased expression of platelet human scavenger receptor class B type I in patients with type 2 diabetes mellitus.
Decreased expression of platelet human scavenger receptor class B type I in patients with type 2 diabetes mellitus.
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DOI：
10.1111/jdi.12158
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发表时间：
2014-05-04
影响因子：
3.2
通讯作者：
Murao K
中科院分区：
文献类型：
--
作者：
Imachi H;Fukata Y;Murao K
糖尿病和前驱糖尿病与血小板和凝血功能紊乱有关。以前，我们已经报道了人清道夫受体B I型（hSR-BI/CLA-1），一种高密度脂蛋白（HDL）的受体，在人血小板表面和血小板内表达1。hSR-BI/CLA-1的表达水平与动脉粥样硬化性疾病患者血小板的胆固醇酯含量和聚集性呈负相关。最近的报道显示，氧化修饰的HDL（OxHDL）通过血小板表达的hSR-BI/CLA-12表现出有效的抗血小板活性。为了测定hSR-BI/CLA-1的表达，将血小板与抗SR-B1/CLA-1豚鼠抗体（5：100稀释）和藻红蛋白（PE）偶联的抗CD 41抗体（Dako Japan，Tokyo，Japan）一起孵育，然后在FACScan系统（Becton Dickinson，圣何塞，CA，USA）上分析荧光细胞，如前所述1。如前所述，使用血小板聚集仪（PA-200; Kowa，Tokyo，Japan），通过同时测量光密度（OD）和激光散射强度（LSI）的最大百分比降低来检查血小板聚集1。与来自年龄匹配的健康志愿者的血小板（HbA 1c [NGSP] 5.6±0.2%）相比，来自22名糖尿病患者的血小板（糖化血红蛋白[HbA 1c;国家糖化血红蛋白标准化计划（NGSP）] 7.9±0.3%;未用药）中hSR-BI/CLA-1的表面表达显著降低（降低约40%）。在腺苷二磷酸（ADP）的情况下，聚集的程度是相似的患者衍生和控制血小板。经100 nmol/LADP刺激后，患者血小板形成的小聚集体明显多于对照组（P< 0.05）。即，在hSR-BI/CLA-1表达量低的血小板中，凝集程度高（表1）。血小板聚集率与HbA 1c显著相关（P< 0.05）。然而，胆固醇酯蓄积和血小板聚集与血浆胆固醇、HDL、低密度脂蛋白（LDL）或甘油三酯水平无显著相关性。这些结果表明，hSR-BI/CLA-1蛋白的丰度与血小板中胆固醇酯含量和ADP刺激的血小板聚集-反映血小板功能的两个参数呈负相关。氧化应激导致产生至少两种影响血小板功能的循环产物-OxLDL和OxHDL。OxLDL-CD 36轴触发血小板活化并促进聚集，而OxHDL及其受体SR-BI/CLA-1似乎提供了限制过度血小板刺激和随后血栓形成事件的天然屏障机制2。最近的报道表明，天然HDL也通过SR-BI抑制血小板聚集。天然HDL、中度氧化HDL和SR-BI配体的抑制作用在SR-BI缺陷型血小板中被消除，但在CD 36缺陷型血小板中没有。Sagel等人4报告称，血小板对聚集剂（如ADP和胶原蛋白）敏感，这一特征在明显糖尿病患者中最为突出，在潜伏性糖尿病患者中中度突出，在前驱糖尿病患者中轻微突出。这些观察结果表明，血小板聚集可能在早期糖尿病中增加，并可能参与糖尿病微血管病变的发展4。今后的研究应进一步探讨hSR-BI/CLA-1在糖尿病中的调控机制。
Diabetes and prediabetic conditions are associated with derangement of platelets and coagulation. Previously, we have reported that human scavenger receptor class B type I (hSR-BI/CLA-1), a receptor for high-density lipoprotein (HDL), is expressed on the surface of and within human platelets1. The levels of hSR-BI/CLA-1 expression are inversely correlated with the cholesterol ester content and aggregation of platelets obtained from patients with atherosclerotic disease. A recent report showed that oxidatively modified HDL (OxHDL) exhibits potent antiplatelet activity through plateletexpressed hSR-BI/CLA-12. To determine the expression of hSR-BI/CLA-1, platelets were incubated with anti-SR-B1/CLA-1 guinea pig antibody (5: 100 dilution) and phycoerythrin (PE)-conjugated anti-CD41 antibody (Dako Japan, Tokyo, Japan), and then fluorescent cells were analyzed on a FACScan system (Becton Dickinson, San Jose, CA, USA) as previously described1. Platelet aggregation was examined by simultaneously measuring the maximum percent decrease in optical density (OD) and laser-light scattering intensity (LSI), using an aggregometer (PA-200; Kowa, Tokyo, Japan), as described previously1. The surface expression of hSR-BI/CLA-1 was significantly lower (approximately 40% decrease) in platelets derived from 22 patients with diabetes mellitus (glycated hemoglobin [HbA1c; National Glycohemoglobin Standardization Program (NGSP)] 7.9±0.3%; no medication) than in those derived from age-matched healthy volunteers (HbA1c [NGSP] 5.6±0.2%). In the absence of adenosine disphosphate (ADP), the degree of aggregation was similar in the patient-derived and control platelets. After stimulation with 100 nmol/L ADP, significantly more small aggregates were formed in the patient-derived platelets than in the control platelets (P< 0.05). In other words, the degree of aggregation was high in platelets expressing low levels of hSR-BI/CLA-1 (Table 1). The platelet aggregation was significantly correlated with HbA1c (P< 0.05). However, cholesterol ester accumulation and platelet aggregation were not significantly correlated with the plasma cholesterol, HDL, low-density lipoprotein (LDL) or triglyceride levels. These results suggest that the abundance of the hSR-BI/CLA-1 protein is inversely correlated with both the cholesterol ester content in and ADP-stimulated aggregation of platelets–two parameters that reflect platelet function. Oxidative stress leads to the generation of at least two circulating products that affect platelet function–OxLDL andOxHDL. The OxLDL–CD36 axis triggers platelet activation and promotes aggregation, whereas OxHDL and its receptor, SR-BI/CLA-1, appear to provide a natural shield mechanism restricting excessive platelet stimulation and subsequent thrombotic events2. Recent reports showed that native HDL also inhibited platelet aggregation through SR-BI. The inhibitory effects of native HDL, moderately oxidized HDL and SR-BI ligands were abolished in SR-BI-deficient platelets, but not in CD36-deficient platelets3. Sagel et al. 4 reported that platelets are sensitive to aggregating agents (eg, ADP and collagen), and this feature is most prominent in patients with frank diabetes, moderately prominent in those with latent diabetes and minimally prominent in those with prediabetes. These observations suggest that platelet aggregation might be increased in early diabetes, and might be involved in the development of diabetic microangiopathy4. Future studies should explore the regulatory mechanisms of hSR-BI/CLA-1 in diabetes mellitus.
影响因子：
20.3
作者：
Valiyaveettil, Manojkumar;Kar, Niladri;Podrez, Eugene A.
通讯作者：
Podrez, Eugene A.
影响因子：
39.2
作者：
SAGEL, J;COLWELL, JA;LAIMINS, M
通讯作者：
LAIMINS, M
DOI：
10.1161/01.atv.0000067429.46333.7b
发表时间：
2003-05-01
影响因子：
8.7
作者：
Imachi, H;Murao, K;Ishida, T
通讯作者：
Ishida, T