Changes in vascular reactivity and endothelial Ca2+ dynamics with chronic low flow.
Changes in vascular reactivity and endothelial Ca2+ dynamics with chronic low flow.
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慢性低流量时血管反应性和内皮 Ca2 动力学的变化。
DOI：
10.1111/micc.12354
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Weber,DavidS
中科院分区：
文献类型：
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作者：
Taylor,MarkS;Choi,Chung-Sik;Bayazid,Leith;Glosemeyer,KatherineE;Baker,CalvinCP;Weber,DavidS
血流的中断促进内皮功能障碍，并使血管易于重塑和动脉粥样硬化。最近的研究结果表明，局部Ca 2+信号的空间和时间调谐沿着内皮是至关重要的血管功能。在这项研究中，我们研究了慢性血流中断是否会导致与血管结构和功能变化相关的动态内皮细胞Ca 2+信号模式的改变。对于这些研究，我们对小鼠的左颈动脉进行手术PL以建立慢性低流量2周;右颈动脉保持开放并作为对照（C）。组织学切片显示PL与C动脉相比显著重塑，包括新生内膜形成。等距力测量显示PL与C动脉中PE诱导的收缩增加，KCl诱导的收缩减少。与C血管相比，PL血管对ACh（10− 8至10− 5 mol/L）的内皮依赖性血管舒张反应显著受损。使用共聚焦成像和自定义分析评价内皮Ca 2+暴露PL动脉中Ca 2+动力学的明显损害，其特征在于活性位点减少和事件截断，对应于衰减的血管舒张。我们的研究结果表明，在发展中的血管疾病的内皮功能障碍的特点可能是不同的变化，在空间和时间模式的本地化Ca 2+信号。
Disruption of blood flow promotes endothelial dysfunction and predisposes vessels to remodeling and atherosclerosis. Recent findings suggest that spatial and temporal tuning of local Ca2+signals along the endothelium is vital to vascular function. In this study, we examined whether chronic flow disruption causes alteration of dynamic endothelial Ca2+signal patterning associated with changes in vascular structure and function. For these studies, we performed surgical PL of the left carotid arteries of mice to establish chronic low flow for 2 weeks; right carotid arteries remained open and served as controls (C). Histological sections showed substantial remodeling of PL compared to C arteries, including formation of neointima. Isometric force measurements revealed increased PE‐induced contractions and decreased KCl‐induced contractions in PL vs C arteries. Endothelium‐dependent vasorelaxation in response to ACh; 10−8to 10−5mol/L) was significantly impaired in PL vs C vessels. Evaluation of endothelial Ca2+using confocal imaging and custom analysis exposed distinct impairment of Ca2+dynamics in PL arteries, characterized by reduction in active sites and truncation of events, corresponding to attenuated vasorelaxation. Our findings suggest that endothelial dysfunction in developing vascular disease may be characterized by distinct shifts in the spatial and temporal patterns of localized Ca2+signals.