Nitric oxide synthase expression and functional response to nitric oxide are both important modulators of circulating angiogenic cell response to angiogenic stimuli.
Nitric oxide synthase expression and functional response to nitric oxide are both important modulators of circulating angiogenic cell response to angiogenic stimuli.
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DOI：
10.1161/atvbaha.110.211581
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Springer ML
中科院分区：
文献类型：
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作者：
Heiss C;Schanz A;Amabile N;Jahn S;Chen Q;Wong ML;Rassaf T;Heinen Y;Cortese-Krott M;Grossman W;Yeghiazarians Y;Springer ML
循环血管生成细胞（CAC），也称为内皮祖细胞，在血管修复中起着不可或缺的作用，在冠状动脉疾病（CAD）中功能受损。一氧化氮（NO）在CAC功能中的作用知之甚少。我们假设CAC迁移向血管生成信号是由NO合酶（NOS）的表达和NO的功能反应。类似于内皮细胞，CAC趋化VEGF被阻断抑制NOS，磷酸肌醇-3激酶，或鸟苷酸环化酶，或通过治疗与NO清除剂。添加NO供体（SNAP）和NOS底物L-精氨酸增加随机细胞迁移（趋化作用）和增强VEGF依赖的趋化性。正常人CACs表达eNOS，而CAD患者CACs不表达eNOS。与健康的CACs相比，患者CACs的趋化性和对VEGF的趋化性均降低，但通过SNAP恢复至健康值。与此同时，CAD患者表现出较低的流量介导的血管舒张和血浆NO源亚硝酸盐比年轻的健康受试者，表明内皮功能障碍与降低NO生物利用度。CAC趋化性需要NOS活性。在CAD患者中，NOS表达和NO生物利用度的受损，而不是对NO的反应，可能导致CAC功能障碍并限制其再生能力。
Circulating angiogenic cells (CACs), also termed endothelial progenitor cells, play an integral role in vascular repair and are functionally impaired in coronary artery disease (CAD). The role of nitric oxide (NO) in CAC function is poorly understood. We hypothesized that CAC migration toward angiogenic signals is modulated by both NO synthase (NOS) expression and functional response to NO. Similar to endothelial cells, CAC chemotaxis to VEGF was blocked by inhibition of NOS, phosphoinositide-3 kinase, or guanylyl cyclase, or by treatment with an NO scavenger. Addition of a NO donor (SNAP) and the NOS-substrate L-arginine increased random cell migration (chemokinesis) and enhanced VEGF-dependent chemotaxis. Healthy CACs expressed eNOS, but eNOS was not detected in CAD patient CACs. Both chemokinesis and chemotaxis to VEGF of patient CACs were decreased compared to healthy CACs, but were restored to healthy values by SNAP. In parallel, CAD patients exhibited lower flow-mediated vasodilation and plasma NO source nitrite than young healthy subjects, indicating endothelial dysfunction with reduced NO bioavailability. NOS activity is required for CAC chemotaxis. In CAD patients, impairment of NOS expression and NO bioavailability, rather than response to NO, may contribute to CAC dysfunction and limit their regenerative capacity.