Endothelial cell response to disturbed flow in diabetic conditions

内皮细胞对糖尿病条件下血流紊乱的反应

基本信息

批准号：
8689563
负责人：
Alisa S Morss Clyne
金额：
$ 38.63万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8689563
关键词：
Acute Address Affect Animals Apical Arterial Fatty Streak Arteries Atherosclerosis Award Awareness Basement membrane Biochemical Biological Availability Biomechanics Biomedical Engineering Blood Blood Glucose Blood Vessels Blood flow Cardiovascular Diseases Cell Adhesion Cell Adhesion Molecules Cell Line Cells Cellular Mechanotransduction Chronic Clinical Trials Collagen Development Diabetes Mellitus Diabetic Angiopathies Disease Education Endothelial Cells Event Functional disorder Future Glucose Goals Growth Health Hyperglycemia Impairment In Vitro Inflammation Inflammatory Intercellular Junctions Laboratories Lead Location Measures Mechanics Metabolic Modeling Morbidity - disease rate Myocardial Infarction Nitric Oxide Oxidative Stress Permeability Phenotype Positioning Attribute Production Protein Kinase C Research Risk Factors Stroke Students Surface Systemic disease Universities Vascular Endothelial Growth Factors Vascular Permeabilities Work atheroprotective blood glucose regulation cadherin 5 career cell injury diabetic diabetic cardiomyopathy experience fluid flow graduate student human NOS3 protein improved monolayer mortality p21 activated kinase prevent public health relevance repaired response shear stress undergraduate student

项目摘要

DESCRIPTION (provided by applicant): People with diabetes experience severe, accelerated atherosclerosis, which leads to heart attack and stroke. Blood sugar control delays diabetic vascular complications, suggesting that blood sugar is a primary risk factor for diabetic cardiovascular disease. However, even in people with diabetes, atherosclerotic plaques still develop in regions where arteries divide or bend. This suggests that blood flow changes at these locations combine with low or high blood sugar to cause diabetic atherosclerosis. Endothelial cells line all blood contacting surfaces in the body. Healthy endothelial cells prevent atherosclerotic plaque formation by controlling blood vessel permeability and inflammation. In both disturbed flow and altered glucose, endothelial cells are dysfunctional and promote atherosclerotic plaque development. While these two conditions have been studied individually, the mechanism by which altered glucose increases atherosclerotic plaque development in disturbed blood flow regions has not yet been studied. Our research goal is to investigate how altered blood sugar and blood flow mechanics interact to cause accelerated atherosclerosis in diabetes. We previously showed that low and high glucose conditions change the way that endothelial cells respond to normal blood flow. In this proposal, our objective is to study low and high glucose effects on endothelial cells in normal or disturbed blood flow. We hypothesize that normal blood flow protects endothelial cells from glucose-induced damage, but that acute glucose changes exacerbate disturbed flow effects. We will involve graduate and undergraduate students in the research through co-operative education opportunities. Successful project completion will clarify how normal blood flow protects endothelial cells and disturbed flow accentuates cell damage. This will improve our understanding of how diabetic atherosclerosis remains a focal disease despite systemic glucose changes. In the future, this will create new therapies for diabetic vascular disease. The will also enhance research opportunities for undergraduate mechanical and biomedical engineering students by providing 6 month co-operative education positions in our cellular mechanotransduction laboratory. These experiences will expand student awareness of biomechanics research diversity while inspiring them to explore health research careers.

描述（由申请人提供）：糖尿病患者经历严重的加速动脉粥样硬化，导致心脏病发作和中风。血糖控制延迟糖尿病血管并发症，表明血糖是糖尿病心血管疾病的主要危险因素。但是，即使在糖尿病患者中，动脉粥样硬化的斑块仍在动脉分裂或弯曲的地区发展。这表明这些位置的血流变化与低血糖或高血糖结合起来引起糖尿病动脉粥样硬化。内皮细胞在体内所有血接触表面。健康的内皮细胞预防通过控制血管渗透性和炎症，动脉粥样硬化斑块形成。在流动障碍和葡萄糖变化中，内皮细胞均功能障碍并促进动脉粥样硬化斑块的发育。虽然已经对这两种疾病进行了分别研究，但尚未研究尚未研究血液流动区域动脉粥样硬化斑块发育的机制。我们的研究目标是研究血糖和血流力学改变如何相互作用，以引起糖尿病的动脉粥样硬化加速。我们先前表明，低葡萄糖条件改变了内皮细胞对正常血流的反应方式。在此提案中，我们的目标是低学习和高葡萄糖对正常或障碍血流中内皮细胞的影响。我们假设正常的血流可保护内皮细胞免受葡萄糖诱导的损伤，但急性葡萄糖会改变加剧了干扰的流动效应。我们将通过合作教育机会让研究生和本科生参与研究。成功的项目完成将阐明正常的血流如何保护内皮细胞并干扰流量会突出细胞损伤。尽管全身性葡萄糖变化，但这将提高我们对糖尿病动脉粥样硬化如何仍然是局灶性疾病的理解。将来，这将为糖尿病血管疾病创造新的疗法。这项将通过在我们的Cellular Mechantotransduction实验室提供6个月的合作教育职位来增加本科机械和生物医学工程专业学生的研究机会。这些经验将扩大学生对生物力学研究多样性的认识，同时激发他们探索健康研究职业。