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的长期目标是确定早期非侵入性成像和血液生物标志物， 脑血管功能障碍和认知健康。具体而言，该项目的目标是界定和 在项目I和II的参与者中表征：1）使用经颅 多普勒超声检查; 2）血液传播的微泡的细胞起源，内容物和血栓形成潜力 使用流式细胞术和血小板功能，使用血小板分泌和活化测定;以及 3)血传微泡特征、血小板功能和脑血管疾病之间的关系 微血管扩张能力与脑结构和认知的变化，如项目I和II所定义。 我们小组的三个独立观察结果为这个项目提供了基础，并为以下因素提供了潜在的联系： 激素状态、血液成分、血管功能和认知。首先，血液传播的数量 血栓前微泡随着绝经期雌激素的减少而增加;第二，扩张能力 绝经期妇女的脑微血管减少;第三，血小板数量 微聚集体与脑白色物质高信号呈正相关，与认知功能呈负相关。 绝经后36个月内的表现。该提案的实验将确定来源， 血液成分和微泡的特性，同时与脑微血管 有心血管疾病和认知能力下降风险的女性的舒张能力， 先兆子痫或绝经期雌激素缺乏。这项研究的结果是独立的，但与以下结果相关联： 项目I和II的总体主题off的SCOR如何女性性别的特定条件的历史 先兆子痫或更年期激素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， 脑微血管扩张能力可以被调节，并与更普遍的发展有关。 女性的心血管疾病