Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress.
Structural Remodeling of Sympathetic Innervation in Atherosclerotic Blood Vessels: Role of Atherosclerotic Disease Progression and Chronic Social Stress.
复制标题
动脉粥样硬化血管交感神经支配的结构重塑：动脉粥样硬化疾病进展和慢性社会压力的作用。
DOI：
10.1097/psy.0000000000000360
复制
发表时间：
2017
影响因子：
3.3
通讯作者：
McCabe,PhilipM
中科院分区：
文献类型：
--
作者：
Noller,CrystalM;Mendez,ArmandoJ;Szeto,Angela;Boulina,Marcia;Llabre,MariaM;Zaias,Julia;Schneiderman,Neil;McCabe,PhilipM
目的交感神经系统 (SNS) 可因行为因素和/或疾病的存在而发生显着的结构可塑性，导致周围组织的 SNS 过度神经支配。 SNS 被认为是压力行为和脉管系统动脉粥样硬化进展之间的重要中介。本研究检查了遗传性高脂血症动脉粥样硬化动物模型——渡边遗传性高脂血症兔（WHHL；相对于血脂正常的新西兰白兔[NZW]）的脉管系统中是否发生了 SNS 的结构重塑，以及 SNS 可塑性是否由疾病进展和/或应激性社会行为驱动。方法将 WHHL 和 NZW 兔分配到不稳定或稳定的社会环境中 4 个月。使用免疫荧光显微镜评估主动脉粥样硬化并量化 SNS 主动脉神经支配。结果在 WHHL 和 NZW 的主动脉中观察到许多 SNS 静脉曲张，延伸至血管中膜和内膜，这是一种先前未报道的神经支配模式。 WHHL 表现出比 NZW 显着更强的神经支配 (F (1, 41) = 55.3, p<. 001)，动脉粥样硬化新内膜具有广泛的神经支配。神经支配密度与 WHHL 中的疾病程度高度相关 (r (21)= 0.855, p<. 001)。社会环境不影响 NZW（主动脉弓：p=.078，胸主动脉：p=.34）或 WHHL（主动脉弓：p=.97，胸主动脉：p=.61）的神经支配。结论研究结果表明，神经支配过度主要是由疾病的进展而不是社会环境驱动的。在动脉粥样硬化的人类和小鼠主动脉中观察到的 SNS 神经支配模式与兔子一致，表明患病血管壁的 SNS 过度神经支配是哺乳动物物种的普遍特征。
ObjectiveThe sympathetic nervous system (SNS) can undergo dramatic structural plasticity in response to behavioral factors and/or the presence of disease, leading to SNS hyperinnervation of peripheral tissues. The SNS has been proposed as an important mediator between stressful behavior and the progression of atherosclerosis in the vasculature. The present study examined whether structural remodeling of the SNS occurs in the vasculature in a genetically hyperlipidemic animal model of atherosclerosis, the Watanabe heritable hyperlipidemic rabbit (WHHL; relative to normolipidemic New Zealand white rabbits [NZW]), and whether SNS plasticity is driven by the progression of disease and/or by stressful social behavior.MethodsWHHL and NZW rabbits were assigned to an unstable or stable social environment for 4 months. Aortic atherosclerosis was assessed and SNS aortic innervation quantified using immunofluorescent microscopy.ResultsNumerous SNS varicosities were observed throughout the aorta in WHHLs and NZWs, extending into the vascular media and intima, an innervation pattern not previously reported. WHHLs exhibited significantly greater innervation than NZWs (F (1, 41)= 55.3, p<. 001), with extensive innervation of the atherosclerotic neointima. The innervation density was highly correlated with the extent of disease in the WHHLs (r (21)= 0.855, p<. 001). Social environment did not influence innervation in NZWs (aortic arch: p=. 078, thoracic aorta: p=. 34) or WHHLs (arch: p=. 97, thoracic: p=. 61).ConclusionsThe findings suggest that hyperinnervation is driven largely by the progression of disease rather than social environment. SNS innervation patterns observed in atherosclerotic human and mouse aortas were consistent with the rabbit, suggesting that SNS hyperinnervation of the diseased vessel wall is a general feature across mammalian species.