气候变化领域集成服务门户(CCPortal): PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity

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DOI	10.1073/pnas.2025998118
	PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity
	Dabertrand F.; Harraz O.F.; Koide M.; Longden T.A.; Rosehart A.C.; Hill-Eubanks D.C.; Joutel A.; Nelson M.T.
发表日期	2021
ISSN	00278424
卷号	118 期号:17
英文摘要	Cerebral small vessel diseases (SVDs) are a central link between stroke and dementia—two comorbidities without specific treatments. Despite the emerging consensus that SVDs are initiated in the endothelium, the early mechanisms remain largely unknown. Deficits in on-demand delivery of blood to active brain regions (functional hyperemia) are early manifestations of the underlying pathogenesis. The capillary endothelial cell strong inward-rectifier K+ channel Kir2.1, which senses neuronal activity and initiates a propagating electrical signal that dilates upstream arterioles, is a cornerstone of functional hyperemia. Here, using a genetic SVD mouse model, we show that impaired functional hyperemia is caused by diminished Kir2.1 channel activity. We link Kir2.1 deactivation to depletion of phosphatidylinositol 4,5-bisphosphate (PIP2), a membrane phospholipid essential for Kir2.1 activity. Systemic injection of soluble PIP2 rapidly restored functional hyperemia in SVD mice, suggesting a possible strategy for rescuing functional hyperemia in brain disorders in which blood flow is disturbed. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	CADASIL; Cerebral small vessel diseases; Functional hyperemia; PIP2; Potassium channel
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179723
作者单位	Department of Pharmacology, Larner College of Medicine, University of Vermont, Burlington, VT 05405, United States; Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States; Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, United States; Vermont Center for Cardiovascular and Brain Health, University of Vermont, Burlington, VT 05405, United States; Institute of Psychiatry and Neurosciences of Paris, INSERM UMR1266, University of Paris, Paris, F-75014, France; Psychiatrie et Neurosciences, Groupe Hospitalier Universitaire Paris, Paris, F-75014, France; Division of Cardiovascular Sciences, University of Manchester, Manchester, M13 9PL, United Kingdom
推荐引用方式 GB/T 7714	Dabertrand F.,Harraz O.F.,Koide M.,et al. PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity[J],2021,118(17).
APA	Dabertrand F..,Harraz O.F..,Koide M..,Longden T.A..,Rosehart A.C..,...&Nelson M.T..(2021).PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity.Proceedings of the National Academy of Sciences of the United States of America,118(17).
MLA	Dabertrand F.,et al."PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity".Proceedings of the National Academy of Sciences of the United States of America 118.17(2021).