Heparanase expression and activity are increased in platelets during clinical sepsis.
Heparanase expression and activity are increased in platelets during clinical sepsis.
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临床败血症期间血小板中肝素酶的表达和活性增加。
DOI：
10.1111/jth.15266
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Rondina MT
中科院分区：
文献类型：
--
作者：
Eustes AS;Campbell RA;Middleton EA;Tolley ND;Manne BK;Montenont E;Rowley JW;Krauel K;Blair A;Guo L;Kosaka Y;Medeiros-de-Moraes IM;Lacerda M;Hottz ED;Neto HCF;Zimmerman GA;Weyrich AS;Petrey A;Rondina MT
乙酰肝素酶（HPSE）是唯一已知的能降解硫酸乙酰肝素的哺乳动物酶。硫酸乙酰肝素蛋白聚糖是糖萼的基本成分，并维持血液和内皮细胞之间的生理屏障。脓毒症期间HPSE增加，这有助于有害的糖萼降解、内皮屏障功能丧失和死亡率。由于血小板是HPSE最丰富的细胞来源之一，我们试图确定在临床脓毒症期间人血小板中HPSE表达和活性是否增加。我们还研究了血小板HPSE表达与临床结果之间的关系。使用互补转录组学、蛋白质组学和功能性酶测定法，在从脓毒症患者（n = 59）分离的血小板中测定HPSE的表达和活性，并且为了比较，在性别匹配的健康供体（n = 46）中测定HPSE的表达和活性。随访脓毒症患者的主要结局死亡率，前瞻性采集脓毒症患者的临床数据。脓毒症患者血小板中HPSE mRNA表达显著增加。核糖体足迹分析，然后[S35]甲硫氨酸标记试验，证明HPSE mRNA翻译和HPSE蛋白合成显着上调血小板在脓毒症。虽然在脓毒症期间血小板中HPSE蛋白的前体和活性形式都增加，但只有HPSE蛋白的活性形式与脓毒症相关死亡率显著相关。与转录组学和蛋白质组学上调一致，HPSE酶活性在脓毒症期间也在血小板中增加。在临床脓毒症期间，血小板中HPSE、翻译和酶活性增加。HPSE蛋白活性形式的表达增加与脓毒症相关死亡率相关。
Heparanase (HPSE) is the only known mammalian enzyme that can degrade heparan sulfate. Heparan sulfate proteoglycans are essential components of the glycocalyx, and maintain physiological barriers between the blood and endothelial cells. HPSE increases during sepsis, which contributes to injurious glyocalyx degradation, loss of endothelial barrier function, and mortality. As platelets are one of the most abundant cellular sources of HPSE, we sought to determine whether HPSE expression and activity increases in human platelets during clinical sepsis. We also examined associations between platelet HPSE expression and clinical outcomes. Expression and activity of HPSE was determined in platelets isolated from septic patients (n = 59) and, for comparison, sex-matched healthy donors (n = 46) using complementary transcriptomic, proteomic, and functional enzymatic assays. Septic patients were followed for the primary outcome of mortality, and clinical data were captured prospectively for septic patients. The mRNA expression of HPSE was significantly increased in platelets isolated from septic patients. Ribosomal footprint profiling, followed by [S35] methionine labeling assays, demonstrated that HPSE mRNA translation and HPSE protein synthesis were significantly upregulated in platelets during sepsis. While both the pro- and active forms of HPSE protein increased in platelets during sepsis, only the active form of HPSE protein significantly correlated with sepsis-associated mortality. Consistent with transcriptomic and proteomic upregulation, HPSE enzymatic activity was also increased in platelets during sepsis. During clinical sepsis HPSE, translation, and enzymatic activity are increased in platelets. Increased expression of the active form of HPSE protein is associated with sepsis-associated mortality.
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影响因子：
3.3
作者：
Eicher JD;Wakabayashi Y;Vitseva O;Esa N;Yang Y;Zhu J;Freedman JE;McManus DD;Johnson AD
通讯作者：
Johnson AD
影响因子：
5.4
作者：
Manon-Jensen, Tina;Multhaupt, Hinke A. B.;Couchman, John R.
通讯作者：
Couchman, John R.
影响因子：
3.2
作者：
Chen, Song;He, Ying;Jin, Guiyun
通讯作者：
Jin, Guiyun
DOI：
10.1164/rccm.200807-1085oc
发表时间：
2009-03-15
影响因子：
24.7
作者：
Freishtat, Robert J.;Natale, JoAnne;Hoffman, Eric P.
通讯作者：
Hoffman, Eric P.
影响因子：
4.4
作者：
Johnson, GB;Brunn, GJ;Platt, JL
通讯作者：
Platt, JL