Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo.
Endothelial surface glycocalyx can regulate flow-induced nitric oxide production in microvessels in vivo.
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DOI：
10.1371/journal.pone.0117133
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Fu BM
中科院分区：
文献类型：
--
作者：
Yen W;Cai B;Yang J;Zhang L;Zeng M;Tarbell JM;Fu BM
由于其独特的位置，在微血管壁的腔侧的内皮表面糖萼（ESG）可以作为血流的机械传感器和换能器，从而调节内皮功能。为了研究ESG的这种作用，我们使用荧光显微镜来测量一氧化氮（NO）的生产在毛细血管后的小静脉和小动脉的大鼠肠系膜下减少（低）和正常（高）的流量条件下，有和没有酶预处理，以去除硫酸乙酰肝素（HS）的ESG和在存在的内皮型一氧化氮合酶（eNOS）抑制剂，NG-单甲基-L-精氨酸（L-NMMA）。将大鼠（SD，250- 300 g）麻醉。将肠系膜从腹腔中轻轻取出，并置于玻璃盖片表面上进行测量。将单个毛细血管后微静脉或微动脉插管，用5 μM的4，5-二氨基荧光素二乙酸酯（一种膜渗透性的NO荧光指示剂）负载45 min，然后在低流量（~300 μm/s）下测定约10 min和在高流量（~1000 μm/s）下测定约60 min的NO产生。在高流量下，eNOS-2-NO荧光强度在15 min内增加到基线的1.27倍，eNOS-2-NO在高流量下持续增加，在60 min内增加到基线的1.53倍。分别与此相反，没有观察到显着增加NO生产切换到高流量60分钟后，当1小时的预处理，50 mU/mL的乙酰肝素酶III降解ESG的应用。在低流量和高流量以及eNOS抑制下，在小动脉中观察到类似的NO产生。我们的研究结果表明，ESG通过其硫酸乙酰肝素激活eNOS参与内皮细胞的机械感受和转导。
Due to its unique location, the endothelial surface glycocalyx (ESG) at the luminal side of the microvessel wall may serve as a mechano-sensor and transducer of blood flow and thus regulate endothelial functions. To examine this role of the ESG, we used fluorescence microscopy to measure nitric oxide (NO) production in post-capillary venules and arterioles of rat mesentery under reduced (low) and normal (high) flow conditions, with and without enzyme pretreatment to remove heparan sulfate (HS) of the ESG and in the presence of an endothelial nitric oxide synthase (eNOS) inhibitor, NG-monomethyl-L-arginine (L-NMMA). Rats (SD, 250–300g) were anesthetized. The mesentery was gently taken out from the abdominal cavity and arranged on the surface of a glass coverslip for the measurement. An individual post-capillary venule or arteriole was cannulated and loaded for 45 min with 5 μM 4, 5-Diaminofluorescein diacetate, a membrane permeable fluorescent indictor for NO, then the NO production was measured for ~10 min under a low flow (~300 μm/s) and for ~60 min under a high flow (~1000 μm/s). In the 15 min after switching to the high flow, DAF-2-NO fluorescence intensity increased to 1.27-fold of its baseline, DAF-2-NO continuously increased under the high flow, to 1.53-fold of its baseline in 60 min. Inhibition of eNOS by 1 mM L-NMMA attenuated the flow-induced NO production to 1.13-fold in 15 min and 1.30-fold of its baseline in 60 min, respectively. In contrast, no significant increase in NO production was observed after switching to the high flow for 60 min when 1 h pretreatment with 50 mU/mL heparanase III to degrade the ESG was applied. Similar NO production was observed in arterioles under low and high flows and under eNOS inhibition. Our results suggest that ESG participates in endothelial cell mechanosensing and transduction through its heparan sulfate to activate eNOS.
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影响因子：
2.8
作者：
Giantsos-Adams, Kristina M.;Koo, Andrew Jia-An;Song, Sukhyun;Sakai, Jiro;Sankaran, Jagadish;Shin, Jennifer H.;Garcia-Cardena, Guillermo;Dewey, C. Forbes, Jr.
通讯作者：
Dewey, C. Forbes, Jr.
DOI：
10.1039/c3ib40199e
发表时间：
2014-03
期刊：
Integrative biology : quantitative biosciences from nano to macro
影响因子：
--
作者：
Ebong EE;Lopez-Quintero SV;Rizzo V;Spray DC;Tarbell JM
通讯作者：
Tarbell JM
影响因子：
3.1
作者：
BAKER, M;WAYLAND, H
通讯作者：
WAYLAND, H
影响因子：
8.7
作者：
Chang, YS;Yaccino, JA;Tarbell, JM
通讯作者：
Tarbell, JM
影响因子：
37.8
作者：
Förstermann, U;Münzel, T
通讯作者：
Münzel, T