A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage.
A novel interaction between soluble epoxide hydrolase and the AT1 receptor in retinal microvascular damage.
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DOI：
10.1016/j.prostaglandins.2020.106449
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发表时间：
2020-06
影响因子：
2.9
通讯作者：
Al-Shabrawey M
中科院分区：
文献类型：
--
作者：
Wang MH;Ibrahim AS;Hsiao G;Tawfik A;Al-Shabrawey M
临床研究表明，肾素-血管紧张素系统（RAS）可能是治疗糖尿病视网膜病变（DR）的一个有希望的治疗靶点。尽管在DIRECT试验中AT 1受体阻滞剂降低了DR的发生率，但它并没有减少DR的进展。缺乏对RAS诱导的视网膜微血管损伤的分子机制的了解是使用RAS阻断剂预防或治疗DR的关键障碍。本研究的目的是探讨血管紧张素II（Ang II）和糖尿病诱导的视网膜微血管损伤中可溶性环氧化物水解酶（sEH）和AT 1受体之间的相互作用。我们证明，Ang II增加视网膜sEH水平，这是由AT 1阻断剂钝化; 11，12-环氧二十碳三烯酸（EET）的管理加剧玻璃体内Ang II诱导的视网膜白蛋白渗漏;而sEH敲除（KO）和阻断减少Ang II诱导的视网膜血管重塑，sEH KO导致视网膜血管渗漏在Ang II-sEH KO小鼠;而sEH KO通过促进视网膜血管内皮生长因子（VEGF）但降低紧密连接蛋白（ZO-1和occludin）的表达而增强糖尿病诱导的视网膜损伤。我们的研究有望提供一种新的策略，即联合使用E2受体阻滞剂和AT 1受体阻滞剂，以预防或减少DR。
Clinical studies have suggested that the renin-angiotensin system (RAS) may be a promising therapeutic target in treating diabetic retinopathy (DR). While AT1 receptor blockade decreased the incidence of DR in the DIRECT trial, it did not reduce the DR progression. Lack of understanding of the molecular mechanism of retinal microvascular damage induced by RAS is a critical barrier to the use of RAS blockade in preventing or treating DR. The purpose of this study is to investigate the interaction between soluble epoxide hydrolase (sEH) and the AT1 receptor in Angiotensin II (Ang II)- and diabetes-induced retinal microvascular damage. We demonstrate that Ang II increases retinal sEH levels, which is blunted by an AT1 blocker; administration of 11,12-epoxyeicosatrienoic acid (EET) exacerbates intravitreal Ang II-induced retinal albumin leakage; while sEH knockout (KO) and blockade reduce Ang II-induced retinal vascular remodeling, sEH KO causes retinal vascular leakage in Ang II-sEH KO mice; and sEH KO potentiates diabetes-induced retinal damage via promoting retinal vascular endothelial growth factor (VEGF) but reducing expression of tight junction proteins (ZO-1 and occludin). Our studies hold the promise of providing a new strategy, the use of combined EETs blockade with AT1 blocker, to prevent or reduce DR.
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影响因子：
5.6
作者：
Bolinger MT;Antonetti DA
通讯作者：
Antonetti DA
影响因子：
4.4
作者：
Capozzi, Megan E.;McCollum, Gary W.;Penn, John S.
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DOI：
10.1124/jpet.105.085605
发表时间：
2005-07-01
影响因子：
3.5
作者：
Fang, X;Hu, SM;Spector, AA
通讯作者：
Spector, AA
影响因子：
6.5
作者：
Ibrahim, Ahmed S.;Elshafey, Sally;Al-Shabrawey, Mohamed
通讯作者：
Al-Shabrawey, Mohamed
DOI：
10.1016/j.bbalip.2014.12.017
发表时间：
2015-03
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ibrahim AS;Tawfik AM;Hussein KA;Elshafey S;Markand S;Rizk N;Duh EJ;Smith SB;Al-Shabrawey M
通讯作者：
Al-Shabrawey M