Endothelial nitric oxide synthase uncoupling: a novel pathway in OSA induced vascular endothelial dysfunction.
Endothelial nitric oxide synthase uncoupling: a novel pathway in OSA induced vascular endothelial dysfunction.
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DOI：
10.1016/j.resp.2014.12.012
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发表时间：
2015-02-01
影响因子：
2.3
通讯作者：
Khayat, Rami N.
中科院分区：
文献类型：
--
作者：
Varadharaj, Saradhadevi;Porter, Kyle;Pleister, Adam;Wannemacher, Jacob;Sow, Angela;Jarjoura, David;Zweier, Jay L.;Khayat, Rami N.
阻塞性睡眠呼吸暂停（OSA）患者血管内皮功能障碍（VED）和心血管疾病的机制尚不清楚。我们进行了一个全面的评价内皮型一氧化氮合酶（eNOS）的功能直接在微循环内皮组织的OSA患者谁有非常低的心血管疾病的危险状态。19名OSA患者在OSA有效治疗前后进行了臀部活检。我们使用共聚焦显微镜测量了微循环内皮中的超氧化物（O2−·）和一氧化氮（NO）。我们评估了NOS抑制剂L-Nitroarginine-Methyl-Ester（L-NAME）和NOS辅因子tetrahydrobiopterin（BH 4）在治疗前后对患者内皮组织中内皮O2−·和NO的影响。我们发现，eNOS在OSA患者治疗前功能失调，是内皮O2−·过度生产的来源。eNOS功能障碍是可逆的，添加BH 4。这些发现为OSA患者的内皮功能障碍提供了一种新的机制，并为治疗OSA患者的心血管风险提供了一种潜在的靶向途径。
The mechanism of vascular endothelial dysfunction (VED) and cardiovascular disease in obstructive sleep apnea (OSA) is unknown. We performed a comprehensive evaluation of endothelial nitric oxide synthase (eNOS) function directly in the microcirculatory endothelial tissue of OSA patients who have very low cardiovascular risk status. Nineteen OSA patients underwent gluteal biopsies before, and after effective treatment of OSA. We measured superoxide (O2−·) and nitric oxide (NO) in the microcirculatory endothelium using confocal microscopy. We evaluated the effect of the NOS inhibitor L-Nitroarginine-Methyl-Ester (L-NAME) and the NOS cofactor tetrahydrobiopterin (BH4) on endothelial O2−· and NO in patient endothelial tissue before and after treatment. We found that eNOS is dysfunctional in OSA patients pre-treatment, and is a source of endothelial O2−· overproduction. eNOS dysfunction was reversible with the addition of BH4. These findings provide a new mechanism of endothelial dysfunction in OSA patients and a potentially targetable pathway for treatment of cardiovascular risk in OSA.
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影响因子：
64.8
作者：
Chen, Chun-An;Wang, Tse-Yao;Varadharaj, Saradhadevi;Reyes, Levy A.;Hemann, Craig;Talukder, M. A. Hassan;Chen, Yeong-Renn;Druhan, Lawrence J.;Zweier, Jay L.
通讯作者：
Zweier, Jay L.
DOI：
10.1073/pnas.74.8.3203
发表时间：
1977-01-01
影响因子：
11.1
作者：
ARNOLD, WP;MITTAL, CK;MURAD, F
通讯作者：
MURAD, F
影响因子：
0.7
作者：
Efremova, L. V.;Alekseeva, A. Yu.;Veiko, N. N.
通讯作者：
Veiko, N. N.
影响因子：
4.8
作者：
Kuzkaya, N;Weissmann, N;Dikalov, S
通讯作者：
Dikalov, S
影响因子：
5.3
作者：
Agewall, S;Henareh, L;Kublickiene, K
通讯作者：
Kublickiene, K