Markers of Cerebrovascular Dysfunction in Women at Risk

高危女性脑血管功能障碍的标志物

基本信息

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
项目类别：
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&apos 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

项目摘要

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的长期目标是识别早期疾病的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。具体来说，该项目的目标是定义和项目 I 和 II 参与者的特征：1) 使用经颅脑微血管扩张能力多普勒超声检查； 2) 血源性微泡的细胞起源、含量和血栓形成潜力使用流式细胞术和血小板功能，使用血小板分泌和激活测定；和 3）血源性微泡特征、血小板功能与脑功能的关系微血管扩张能力随脑结构和认知的变化而变化，如项目 I 和 II 中所定义。我们小组的三个独立观察结果为该项目以及之间的潜在联系提供了基础荷尔蒙状态、血源性元素、血管功能和认知。一、血源性数量更年期时，促血栓微泡随着雌激素的减少而增加；二、拖延能力更年期女性的脑微血管减少；第三，血小板数量微聚集体与大脑白质高信号呈正相关，与认知呈负相关绝经后36个月内的表现。该提案的实验将定义来源和同时检测血液成分和微泡的特征，以及脑微血管根据以下病史，有心血管疾病风险和认知能力下降的女性的拖延能力先兆子痫或绝经期雌激素缺乏。这项研究的结果独立存在，但与以下结果相关项目 I 和 II 的总体主题是 SCOR 的女性特定性别的历史条件先兆子痫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脑微血管扩张能力可以被调节，并且更普遍地与女性心血管疾病。