Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction.
Depletion of circulating blood NOS3 increases severity of myocardial infarction and left ventricular dysfunction.
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循环血液NOS3的耗竭会增加心肌梗塞的严重程度和左心室功能障碍。
DOI：
10.1007/s00395-013-0398-1
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发表时间：
2014-01
影响因子：
9.5
通讯作者：
Kelm M
中科院分区：
文献类型：
--
作者：
Merx MW;Gorressen S;van de Sandt AM;Cortese-Krott MM;Ohlig J;Stern M;Rassaf T;Gödecke A;Gladwin MT;Kelm M
内皮型一氧化氮合酶3（endothelial NO synthase，NOS 3）的一氧化氮（Nitric oxide，NO）在心肌缺血/再灌注损伤中起重要作用。循环血细胞的亚群，包括红细胞（RBC），携带NOS 3，有助于血压调节和RBC亚硝酸盐/硝酸盐形成。我们假设循环血液中的NOS 3也调节疾病模型中心肌梗死的严重程度。我们将野生型和NOS 3 −/−小鼠的骨髓与野生型小鼠交叉移植，产生仅在血管内皮（BC−/EC+）或血细胞和血管内皮（BC+/EC+）中表达NOS 3的嵌合体。在60分钟的闭胸冠状动脉闭塞24小时再灌注后，心脏功能，梗死面积（IS），NOx水平，红细胞NO形成，红细胞变形性和血管反应性进行了评估。在基线时，BC−/EC+嵌合体的血浆中亚硝酸盐水平较低（BC−/EC+：2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; *p < 0.05），降低RBC内的IFN-γ相关荧光（BC−/EC+：538.4 ± 12.8平均荧光强度（MFI）vs. BC+/EC+：619.6 ± 6.9 MFI; *p < 0.001）和受损的红细胞变形能力（BC-/EC+：0.33 ± 0.01伸长指数（EI）vs. BC+/EC+：0.36 ± 0.06 EI; *p < 0.05），而血管反应性未受影响。风险区域没有差异，但BC−/EC+组的梗死面积更大（BC−/EC+：26 ± 3%; BC+/EC+：14 ± 2%; **p < 0.01），导致射血分数降低（BC−/EC+ 46 ± 2% vs. BC+/EC+：52 ± 2%; *p < 0.05）和收缩末期容积增加。NOS抑制剂S-乙基异硫脲氢溴酸盐的应用与BC+/EC+小鼠的较大梗死面积相关，而BC−/EC+小鼠的梗死面积未受影响。减少梗死面积，保存心脏功能，红细胞中的NO水平和红细胞变形性表明循环NOS 3在嵌合小鼠心肌I/R急性模型中的调节作用。本文的在线版本（doi：10.1007/s 00395 -013-0398-1）包含补充材料，可供授权用户使用。
Nitric oxide (NO) derived from endothelial NO synthase (NOS3) plays a central role in myocardial ischemia/reperfusion (I/R)-injury. Subsets of circulating blood cells, including red blood cells (RBCs), carry a NOS3 and contribute to blood pressure regulation and RBC nitrite/nitrate formation. We hypothesized that the circulating blood born NOS3 also modulates the severity of myocardial infarction in disease models. We cross-transplanted bone marrow in wild-type and NOS3−/− mice with wild-type mice, producing chimeras expressing NOS3 only in vascular endothelium (BC−/EC+) or in both blood cells and vascular endothelium (BC+/EC+). After 60-min closed-chest coronary occlusion followed by 24 h reperfusion, cardiac function, infarct size (IS), NOx levels, RBCs NO formation, RBC deformability, and vascular reactivity were assessed. At baseline, BC−/EC+ chimera had lower nitrite levels in blood plasma (BC−/EC+: 2.13 ± 0.27 μM vs. BC+/EC+ 3.17 ± 0.29 μM; *p < 0.05), reduced DAF FM associated fluorescence within RBCs (BC−/EC+: 538.4 ± 12.8 mean fluorescence intensity (MFI) vs. BC+/EC+: 619.6 ± 6.9 MFI; ***p < 0.001) and impaired erythrocyte deformability (BC−/EC+: 0.33 ± 0.01 elongation index (EI) vs. BC+/EC+: 0.36 ± 0.06 EI; *p < 0.05), while vascular reactivity remained unaffected. Area at risk did not differ, but infarct size was higher in BC−/EC+ (BC−/EC+: 26 ± 3 %; BC+/EC+: 14 ± 2 %; **p < 0.01), resulting in decreased ejection fraction (BC−/EC+ 46 ± 2 % vs. BC+/EC+: 52 ± 2 %; *p < 0.05) and increased end-systolic volume. Application of the NOS inhibitor S-ethylisothiourea hydrobromide was associated with larger infarct size in BC+/EC+, whereas infarct size in BC−/EC+ mice remained unaffected. Reduced infarct size, preserved cardiac function, NO levels in RBC and RBC deformability suggest a modulating role of circulating NOS3 in an acute model of myocardial I/R in chimeric mice. The online version of this article (doi:10.1007/s00395-013-0398-1) contains supplementary material, which is available to authorized users.
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影响因子：
9.5
作者：
Krusche CA;Holthöfer B;Hofe V;van de Sandt AM;Eshkind L;Bockamp E;Merx MW;Kant S;Windoffer R;Leube RE
通讯作者：
Leube RE
DOI：
10.1073/pnas.97.21.11482
发表时间：
2000-10-10
影响因子：
11.1
作者：
Gladwin, MT;Shelhamer, JH;Cannon, RO
通讯作者：
Cannon, RO
DOI：
10.1152/ajpheart.1999.276.5.h1567
发表时间：
1999-05-01
影响因子：
4.8
作者：
Jones, SP;Girod, WG;Lefer, DJ
通讯作者：
Lefer, DJ
影响因子：
20.3
作者：
Dejam, A;Hunter, CJ;Schechter, AN
通讯作者：
Schechter, AN
影响因子：
82.9
作者：
Cosby, K;Partovi, KS;Gladwin, MT
通讯作者：
Gladwin, MT