Lipoxin A4 mediates aortic contraction via RHOA/RHO kinase, endothelial dysfunction and reactive oxygen species.
Lipoxin A4 mediates aortic contraction via RHOA/RHO kinase, endothelial dysfunction and reactive oxygen species.
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DOI：
10.1159/000371490
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发表时间：
2014
影响因子：
1.7
通讯作者：
Webb RC
中科院分区：
文献类型：
--
作者：
Wenceslau CF;McCarthy CG;Szasz T;Webb RC
脂氧素A4（LXA 4）是由花生四烯酸通过脂氧合酶作用产生的生物活性产物。阿司匹林通过乙酰化环氧合酶-2增强脂氧素的产生，其机制称为“阿司匹林触发的脂氧素”。LXA 4具有抗炎和促炎作用，后者与阿司匹林治疗的患者冠状动脉成形术后的再闭塞和再狭窄有关。然而，人们对LXA 4对血管系统的作用知之甚少。我们假设LXA 4促进收缩反应并导致内皮功能障碍。我们使用Wistar大鼠的主动脉来评估血管功能。活性氧（ROS）的生产和收缩和调节蛋白进行了研究。LXA 4通过甲酰肽受体-2激活诱导浓度依赖性收缩，RhoA/Rho激酶抑制剂和ROS清除剂均降低了这种收缩。此外，内皮去除和考克斯-2和NAD（P）H氧化酶抑制剂减弱LXA 4诱导的收缩。LXA 4增强苯肾上腺素诱导的收缩，抑制乙酰胆碱诱导的舒张。在LXA 4存在下，ROS产生增加，RhoA、磷酸化肌球蛋白轻链、考克斯-2和p67 phox的蛋白表达增加。LXA 4在血管系统中具有功能性作用，并且在其产生加剧的情况下可能导致进一步的血管损伤，例如在用阿司匹林治疗的血管成形术相关并发症中。
Lipoxin A4 (LXA4) is a biologically active product generated from arachidonic acid by lipoxygenase action. The production of lipoxins is enhanced by aspirin through acetylation of cyclooxygenase-2, via a mechanism known as “aspirin-triggered lipoxin”. LXA4 has both anti-inflammatory and proinflammatory actions, the latter being related with reocclusion and restenosis after coronary angioplasty in patients treated with aspirin. However, little is known of the actions of LXA4 on the vasculature. We hypothesized that LXA4 promotes contractile responses and contributes to endothelial dysfunction. We used aorta from Wistar rats to assess vascular function. Reactive oxygen species (ROS) production and contractile and regulatory proteins were investigated. LXA4 induced concentration-dependent contractions via formyl peptide receptor-2 activation and both RhoA/Rho kinase inhibitor and ROS scavenger decreased this contraction. Also, endothelium removal, and COX-2 and NAD(P)H oxidase inhibitors attenuate the LXA4-induced contraction. LXA4 potentiated phenylephrine-induced contraction and inhibited acetylcholine-induced relaxation. In the presence of LXA4, ROS production was increased and protein expression of RhoA, phospho-myosin light chain, COX-2 and p67phox was higher. LXA4 has a functional role in the vasculature and may contribute to further vascular damage in conditions where its production is exacerbated, such as in angioplasty-associated complications treated with aspirin.
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影响因子：
4.4
作者：
Wu, Yan;Zhai, Heng;Shang, You
通讯作者：
Shang, You
影响因子：
37.8
作者：
BREZINSKI, DA;NESTO, RW;SERHAN, CN
通讯作者：
SERHAN, CN
影响因子：
--
作者：
BODE, SM;KUHN, M;FORSTERMANN, U
通讯作者：
FORSTERMANN, U
影响因子：
4.9
作者：
Wenceslau, Camilla F.;Rossoni, Luciana V.
通讯作者：
Rossoni, Luciana V.
DOI：
10.1096/fj.10-159913
发表时间：
2010-11
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Maderna P;Cottell DC;Toivonen T;Dufton N;Dalli J;Perretti M;Godson C
通讯作者：
Godson C