NAD(P)H oxidase and eNOS play differential roles in cytomegalovirus infection-induced microvascular dysfunction.
NAD(P)H oxidase and eNOS play differential roles in cytomegalovirus infection-induced microvascular dysfunction.
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DOI：
10.1016/j.freeradbiomed.2011.09.039
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发表时间：
2011-12-15
影响因子：
7.4
通讯作者：
Stokes, Karen Y.
中科院分区：
文献类型：
--
作者：
Leskov, Igor L.;Whitsett, Jennifer;Vasquez-Vivar, Jeannette;Stokes, Karen Y.
关键词：
原发性巨细胞病毒（CMV）感染促进氧化应激，降低内皮细胞中一氧化氮（NO）的生物利用度。这些事件是对心血管危险因素的最早血管反应之一。我们评估了NAD（P）H氧化酶和NO生物利用度在单独或合并高胆固醇血症的持续CMV感染的微血管反应中的作用。野生型（WT）或gp 91 phox（NAD（P）H氧化酶亚基）敲除小鼠在接受正常或高胆固醇饮食（−HC）前5周接受模拟接种物或3× 104 PFU鼠CMV（mCMV）IP，持续4周，然后使用活体显微镜评估小动脉功能和小静脉血细胞募集。一些WT组接受sepiapterin（一氧化氮合酶辅因子的前体，四氢生物蝶呤）或夹竹桃麻素（NAD（P）H氧化酶抑制剂/抗氧化剂）。无论饮食如何，mCMV与mock WT相比，内皮依赖性血管舒张受损。这不受sepiapterin的影响，并且一氧化氮合酶的药理学抑制在Mock和mCMV小鼠中类似地减少扩张。夹竹桃素或缺乏总的，但不仅是血细胞或血管壁（使用骨髓嵌合体测试），gp 91 phox防止小动脉功能障碍。血细胞募集由mCMV-HC诱导。Sepiapterin，但不是NAD（P）H氧化酶缺乏/夹竹桃素，减少白细胞的积累，而血小板粘附减少sepiapterin，夹竹桃素或总，血小板特异性或血管壁gp 91 phox缺陷。这些数据表明，造血和血管壁NAD（P）H氧化酶在mCMV诱导的小动脉功能障碍中活化，血小板和血管NAD（P）H氧化酶在mCMV-HC诱导的血栓形成表型中活化。相比之下，sepiapterin的发现表明eNOS功能障碍，可能解偶联，介导小静脉而不是小动脉对mCMV-HC的反应，因此表明NAD（P）H氧化酶和eNOS差异调节对mCMV的微血管反应。
Primary cytomegalovirus (CMV) infection promotes oxidative stress and reduces nitric oxide (NO) bioavailability in endothelial cells. These events are among the earliest vascular responses to cardiovascular risk factors. We assessed the roles of NAD(P)H oxidase and NO bioavailability in microvascular responses to persistent CMV infection alone or with hypercholesterolemia. Wildtype (WT) or gp91phox (NAD(P)H oxidase subunit) knockout mice received mock-inoculum or 3×104PFU murine CMV (mCMV) IP 5wks before placement on normal or high cholesterol diet (−HC) for 4wks before assessment of arteriolar function and venular blood cell recruitment using intravital microscopy. Some WT groups received sepiapterin (a precursor of the nitric oxide synthase co-factor, tetrahydrobiopterin), or apocynin (NAD(P)H oxidase inhibitor/antioxidant). Endothelium-dependent vasodilation was impaired in mCMV vs. mock WT, regardless of diet. This was not affected by sepiapterin, and pharmacological inhibition of nitric oxide synthase reduced dilation similarly in Mock and mCMV mice. Apocynin or deficiency of total, but not only blood cell or vascular wall (tested using bone marrow chimeras), gp91phox protected against arteriolar dysfunction. Blood cell recruitment was induced by mCMV-HC. Sepiapterin, but not NAD(P)H oxidase deficiency/apocynin, reduced leukocyte accumulation, whereas platelet adhesion was reduced by sepiapterin, apocynin or total, platelet-specific or vascular wall gp91phox-deficiency. These data implicate activation of both hematopoietic and vessel wall NAD(P)H oxidase in mCMV-induced arteriolar dysfunction, and platelet and vascular NAD(P)H oxidase in the thrombogenic phenotype induced by mCMV-HC. In contrast, findings with sepiapterin suggest eNOS dysfunction, perhaps uncoupling, mediates venular, but not arteriolar, responses to mCMV-HC, thus indicating that NAD(P)H oxidase and eNOS differentially regulate microvascular responses to mCMV.
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影响因子：
37.8
作者：
Dixon, LJ;Morgan, DR;McVeigh, GE
通讯作者：
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影响因子：
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DOI：
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