Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis.
Proteoglycan 4 (lubricin) is a highly sialylated glycoprotein associated with cardiac valve damage in animal models of infective endocarditis.
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蛋白聚糖 4（润滑素）是一种高度唾液酸化的糖蛋白，与感染性心内膜炎动物模型中的心脏瓣膜损伤相关。
DOI：
10.1093/glycob/cwab095
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发表时间：
2021
期刊：
影响因子：
4.3
通讯作者：
Bensing,BarbaraA
中科院分区：
文献类型：
--
作者：
Solakyildirim,Kemal;Li,Yi;Bayer,ArnoldS;Sullam,PaulM;Xiong,YanQ;Lebrilla,CarlitoB;Bensing,BarbaraA
戈登链球菌和血链球菌是牙齿表面的主要定植菌，通常与口腔健康相关，但也可引起感染性心内膜炎 (IE)。这些物种表达“Siglec 样”粘附素，可与宿主糖蛋白上的唾液酸化聚糖结合，从而有助于在心脏瓣膜表面形成受感染的血小板-纤维蛋白血栓（赘生物）。我们之前确定了S的能力。在 IE 动物模型中，相对于唾液酸化核心 2O-聚糖结构的识别，gordoniito 结合唾液酸 T 抗原 (sTa) 增加了致病性。然而，尚不清楚 sTa 结构何时何地展示，以及哪些 sTa 修饰的宿主因子促进瓣膜定植。在这项研究中，我们在该疾病的大鼠和兔模型的主动脉瓣赘生物和血浆中鉴定了唾液酸化糖蛋白。通过使用链球菌 Siglec 样粘附素的重组形式进行凝集素印迹和亲和捕获，鉴定显示 sTa 与核心 2O-聚糖结构的糖蛋白，并通过质谱分析对 O 连接聚糖进行分析。蛋白多糖 4 (PRG4)，也称为润滑素，是受感染植被中 sTa 的主要载体。此外，与健康动物相比，瓣膜受损或感染的动物的血浆 PRG4 水平显着更高。综合结果表明，除了血小板 GPIbα 之外，PRG4 是在主动脉瓣赘生物中发现的一种高度唾液酸化的粘蛋白样糖蛋白，可能有助于口腔链球菌在这个受保护的血管内生态位中的持续存在。此外，血浆PRG4可以作为心内膜损伤和感染的生物标志物。
Streptococcus gordoniiandStreptococcus sanguinisare primary colonizers of tooth surfaces and are generally associated with oral health, but can also cause infective endocarditis (IE). These species express “Siglec-like” adhesins that bind sialylated glycans on host glycoproteins, which can aid the formation of infected platelet–fibrin thrombi (vegetations) on cardiac valve surfaces. We previously determined that the ability ofS. gordoniito bind sialyl T-antigen (sTa) increased pathogenicity, relative to recognition of sialylated core 2O-glycan structures, in an animal model of IE. However, it is unclear when and where the sTa structure is displayed, and which sTa-modified host factors promote valve colonization. In this study, we identified sialylated glycoproteins in the aortic valve vegetations and plasma of rat and rabbit models of this disease. Glycoproteins that display sTa vs. core 2O-glycan structures were identified by using recombinant forms of the streptococcal Siglec-like adhesins for lectin blotting and affinity capture, and theO-linked glycans were profiled by mass spectrometry. Proteoglycan 4 (PRG4), also known as lubricin, was a major carrier of sTa in the infected vegetations. Moreover, plasma PRG4 levels were significantly higher in animals with damaged or infected valves, as compared with healthy animals. The combined results demonstrate that, in addition to platelet GPIbα, PRG4 is a highly sialylated mucin-like glycoprotein found in aortic valve vegetations and may contribute to the persistence of oral streptococci in this protected endovascular niche. Moreover, plasma PRG4 could serve as a biomarker for endocardial injury and infection.
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戈登链球菌富含丝氨酸的表面糖蛋白 GspB 在感染性心内膜炎发病机制中的作用。
影响因子：
3.8
作者：
Xiong,YanQ;Bensing,BarbaraA;Bayer,ArnoldS;Chambers,HenryF;Sullam,PaulM
通讯作者：
Sullam,PaulM
组织因子是兔肠球菌性心内膜炎赘生物形成的主要刺激因素。
DOI：
10.1172/jci111383
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Drake,TA;Rodgers,GM;Sande,MA
通讯作者：
Sande,MA
影响因子：
3.1
作者：
Takahashi, Y;Takashima, E;Konishi, K
通讯作者：
Konishi, K
影响因子：
4
作者：
Das, Nabangshu;Schmidt, Tannin A.;Dufour, Antoine
通讯作者：
Dufour, Antoine
影响因子：
4.3
作者：
Bensing, Barbara A.;Khedri, Zahra;Sullam, Paul M.
通讯作者：
Sullam, Paul M.