Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release.
Intermittent Hypoxia-Induced Activation of Endothelial Cells Is Mediated via Sympathetic Activation-Dependent Catecholamine Release.
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DOI：
10.3389/fphys.2021.701995
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发表时间：
2021
影响因子：
4
通讯作者：
Mutlu GM
中科院分区：
文献类型：
--
作者：
Cetin-Atalay R;Meliton AY;Wu D;Woods PS;Sun KA;Peng YJ;Nanduri J;Su X;Fang Y;Hamanaka RB;Prabhakar N;Mutlu GM
阻塞性睡眠呼吸暂停（OSA）是一种常见的呼吸障碍，影响了相当大比例的成年人。OSA是心血管疾病（CVD）的独立危险因素;然而，其潜在机制尚未完全了解。由于缺氧的严重程度与某些心血管效应相关，因此间歇性缺氧（IH）被认为是OSA可能导致CVD的机制之一。在这里，我们研究了IH对内皮细胞（EC）活化的影响，其特征在于炎症基因的表达，这是已知的CVD的发病机制中发挥重要作用。C57 BL/6小鼠暴露于IH导致主动脉EC活化，而EC在体外暴露于IH未能做到这一点，表明IH不直接诱导EC活化，而是间接诱导。IH的后果之一是激活交感神经系统和释放儿茶酚胺。我们发现，小鼠暴露于IH引起循环水平的儿茶酚胺升高。通过药理学抑制或肾上腺切除术或颈动脉体消融术抑制IH诱导的儿茶酚胺增加，防止了小鼠中IH诱导的EC激活。支持的关键作用，儿茶酚胺，肾上腺素单独足以引起EC激活在体内和体外。总之，这些结果表明，IH不直接诱导EC活化，但通过释放儿茶酚胺间接诱导EC活化。这些结果表明，针对IH诱导的交感神经活动和儿茶酚胺释放可能是一个潜在的治疗目标，以减轻OSA的CV效应。
Obstructive sleep apnea (OSA) is a common breathing disorder affecting a significant percentage of the adult population. OSA is an independent risk factor for cardiovascular disease (CVD); however, the underlying mechanisms are not completely understood. Since the severity of hypoxia correlates with some of the cardiovascular effects, intermittent hypoxia (IH) is thought to be one of the mechanisms by which OSA may cause CVD. Here, we investigated the effect of IH on endothelial cell (EC) activation, characterized by the expression of inflammatory genes, that is known to play an important role in the pathogenesis of CVD. Exposure of C57BL/6 mice to IH led to aortic EC activation, while in vitro exposure of ECs to IH failed to do so, suggesting that IH does not induce EC activation directly, but indirectly. One of the consequences of IH is activation of the sympathetic nervous system and catecholamine release. We found that exposure of mice to IH caused elevation of circulating levels of catecholamines. Inhibition of the IH-induced increase in catecholamines by pharmacologic inhibition or by adrenalectomy or carotid body ablation prevented the IH-induced EC activation in mice. Supporting a key role for catecholamines, epinephrine alone was sufficient to cause EC activation in vivo and in vitro. Together, these results suggested that IH does not directly induce EC activation, but does so indirectly via release of catecholamines. These results suggest that targeting IH-induced sympathetic nerve activity and catecholamine release may be a potential therapeutic target to attenuate the CV effects of OSA.
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影响因子：
4.3
作者：
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