Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells.
Soluble amyloid-beta, effect on cerebral arteriolar regulation and vascular cells.
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DOI：
10.1186/1750-1326-5-15
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发表时间：
2010-04-13
影响因子：
15.1
通讯作者：
Holtzman DM
中科院分区：
文献类型：
--
作者：
Dietrich HH;Xiang C;Han BH;Zipfel GJ;Holtzman DM
有证据表明，可溶性β淀粉样蛋白（Aβ）具有血管活性，可能导致阿尔茨海默病和脑淀粉样血管病患者的脑血管功能障碍。尚未研究可溶性Aβ对穿透性脑小动脉（主要负责控制脑血管阻力的血管）的影响。新鲜溶解的Aβ1-40和Aβ1-42（而非反向肽Aβ40-1）使大鼠离体穿通小动脉收缩，并减少对三磷酸腺苷（ATP）的扩张。Aβ1-42还增强ATP诱导的血管收缩。Aβ1-40可减弱小动脉肌源性反应，抗A β抗体可减少Aβ1-40诱导的小动脉收缩。Tg 2576小鼠血管中的Aβ长期暴露导致对ATP诱导的血管反应具有显著的年龄依赖性效应。来自6月龄Tg 2576小鼠的血管具有降低的血管反应，而这些在12月龄动物中不存在。Aβ1-40和Aβ1-42可使培养的大鼠微血管细胞产生活性氧（ROS）。自由基清除剂MnTBAP减弱了Aβ诱导的氧化应激和Aβ1-40诱导的大鼠小动脉收缩。我们的研究结果表明，可溶性Aβ1-40和Aβ1-42直接影响离体啮齿动物穿通小动脉的血管调节，ROS部分介导这些作用。一旦存在不溶性Aβ沉积物，小动脉反应性就会大大降低。
Evidence indicates that soluble forms of amyloid-β (Aβ) are vasoactive, which may contribute to cerebrovascular dysfunction noted in patients with Alzheimer's Disease and cerebral amyloid angiopathy. The effects of soluble Aβ on penetrating cerebral arterioles - the vessels most responsible for controlling cerebrovascular resistance - have not been studied. Freshly dissolved Aβ1-40 and Aβ1-42, but not the reverse peptide Aβ40-1 constricted isolated rat penetrating arterioles and diminished dilation to adenosine tri-phosphate (ATP). Aβ1-42 also enhanced ATP-induced vessel constriction. Aβ1-40 diminished arteriolar myogenic response, and an anti-Aβ antibody reduced Aβ1-40 induced arteriolar constriction. Prolonged Aβ exposure in vessels of Tg2576 mice resulted in a marked age-dependent effect on ATP-induced vascular responses. Vessels from 6 month old Tg2576 mice had reduced vascular responses whereas these were absent from 12 month old animals. Aβ1-40 and Aβ1-42 acutely increased production of reactive oxygen species (ROS) in cultured rat cerebro-microvascular cells. The radical scavenger MnTBAP attenuated this Aβ-induced oxidative stress and Aβ1-40-induced constriction in rat arterioles. Our results suggest that soluble Aβ1-40 and Aβ1-42 directly affect the vasomotor regulation of isolated rodent penetrating arterioles, and that ROS partially mediate these effects. Once insoluble Aβ deposits are present, arteriolar reactivity is greatly diminished.
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DOI：
10.1523/jneurosci.4686-08.2008
发表时间：
2008-12-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Han BH;Zhou ML;Abousaleh F;Brendza RP;Dietrich HH;Koenigsknecht-Talboo J;Cirrito JR;Milner E;Holtzman DM;Zipfel GJ
通讯作者：
Zipfel GJ
影响因子：
1.7
作者：
Jung, SS;Van Nostrand, WE
通讯作者：
Van Nostrand, WE
DOI：
10.1097/00004647-200012000-00005
发表时间：
2000-12-01
影响因子：
6.3
作者：
Niwa, K;Carlson, GA;Iadecola, C
通讯作者：
Iadecola, C
影响因子：
82.9
作者：
Deane, R;Yan, SD;Zlokovic, B
通讯作者：
Zlokovic, B
影响因子：
3.3
作者：
Matos, M.;Augusto, E.;Agostinho, P.
通讯作者：
Agostinho, P.