Markers of Cerebrovascular Dysfunction in Women at Risk

高危女性脑血管功能障碍的标志物

• 批准号: 8927523
• 负责人: VIRGINIA M MILLER
• 金额: $ 27.8万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8927523
• 关键词: Affect; Age; Alzheimer' s Disease; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Area; Biological Assay; Biological Markers; Blood; Blood Platelets; Blood Vessels; Blood coagulation; Blood flow; Brain; Brain Pathology; Cardiovascular Diseases; Cardiovascular system; Cells; Cerebrum; Characteristics; Cognition; Cognition Disorders; Cognitive; Data; Decision Making; Dementia; Development; Disease; Eclampsia; Elements; Endothelial Cells; Epidemiology; Estrogens; Event; Female; Flow Cytometry; Functional disorder; Goals; Health; Hormonal; Hormones; Impaired cognition; Incidence; Laboratories; Life; Link; Measures; Membrane; Menopause; Monitor; Nature; Neurons; Participant; Patient Self-Report; Physicians; Platelet Activation; Platelet Count measurement; Population; Postmenopause; Pre-Eclampsia; Pregnancy; Premenopause; Prevention; Recording of previous events; Risk; Sex Characteristics; Source; Stress Tests; Stroke; Structure; Testing; Time; Transcranial Doppler Ultrasonography; Vascular Diseases; Vascular blood supply; Vasospasm; Vesicle; White Matter Hyperintensity; Woman; base; blood pressure reduction; cardiovascular disorder risk; cell injury; cerebrovascular; cognitive capacity; cognitive performance; cohort; design; endothelial dysfunction; hormone therapy; middle age; non-invasive imaging; novel; pregnancy disorder; research study; sex; sex risk; targeted treatment; vascular endothelial dysfunction

The long-term goal of Project III is to identify non-invasive imaging and blood biomarkers of eariy cerebrovascular dysfunction and cognitive health. Specifically, aims of this project are to define and characterize in participants of Projects I and II: 1) cerebral microvascular dilatory capacity using transcranial Doppler ultrasonography; 2) the cellular origin, content, and thrombotic potential of blood-borne microvesicles using flow cytometry and platelet functions using assays for platelet secretion and activation; and 3) relationships among characteristics of blood-borne microvesicles, platelet functions, and cerebral microvascular dilatory capacity with changes in brain stmeture and cognition, as defined in Projects I and II. Three independent observations from our group provide the basis for this project and potential links among hormonal status, blood-borne elements, vascular function, and cognition. First, numbers of blood-borne prothrombotic microvesicles increase with decreases in estrogen at menopause; second, the dilatory capacity of the cerebral microvasculature decreases in women at menopause; and third, numbers of platelet microaggregates correlate positively with brain white matter hyperintensities and negatively with cognitive performance within 36 months of menopause. Experiments of this proposal will define sources and characteristics of blood elements and microvesicles simultaneously, together with cerebral microvascular dilatory capacity in women at risk for cardiovascular disease and cognitive decline based on either a history of preeclampsia or estrogen deficiency at menopause. Results of this study stand on their own but link results of Projects I and II to the overarching theme oif the SCOR of how female sex-specific conditions of a history preeclampsia or menopausal hormonal status affect cognition through changes in cerebrovascular function. Furthermore, assessment of platelet and microvesicle characteristics provides potential mechanisms by which cerebral microvascular dilatory capacity could be modulated and associate more generally with development of cardiovascular disease in women.

项目III的长期目标是识别无创成像和Eariy的血液生物标志物 脑血管功能障碍和认知健康。具体而言，该项目的目的是定义和 在项目I和II的参与者中表征：1）使用经颅的脑微血管膨胀能力 多普勒超声检查； 2）血液传播微泡的细胞起源，含量和血小板潜力 使用流式细胞仪和血小板功能，使用测定血小板分泌和激活；和 3）血传播微泡，血小板功能和脑的特征之间的关系 微血管膨胀能力随脑染色和认知的变化而变化，如项目I和II所定义。 我们小组的三个独立观察为该项目提供了基础，并在 激素状态，血传播元素，血管功能和认知。首先，血源数量 促血栓形成的微囊泡随年后时的雌激素减少而增加。其次，扩张能力 在更年期，女性的脑微脉管系统减少了；第三，血小板数量 微聚集与脑白质超强度正相关，并与认知呈负相关 更年期36个月内的表现。该提案的实验将定义来源和 血液元素和微泡的特征，同时与脑微血管一起 基于这两种历史的病史 更年期的先兆子痫或雌激素缺乏症。这项研究的结果是自己的，但链接的结果 项目I和II的总体主题是史的分数 子痫前期或更年期荷尔蒙状态通过脑血管功能的变化影响认知。 此外，血小板和微泡特征的评估提供了潜在的机制 可以调节脑微血管扩张能力，并更普遍地与 女性心血管疾病。