Endothelial cell response to disturbed flow in diabetic conditions

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。血糖控制可延缓糖尿病血管并发症，提示血糖是糖尿病心血管疾病的主要危险因素。然而，即使在糖尿病患者中，动脉粥样硬化斑块仍然在动脉分裂或弯曲的区域发展。这表明，这些部位的血流变化联合收割机与低血糖或高血糖相结合，导致糖尿病动脉粥样硬化。 内皮细胞排列在体内所有血液接触表面。健康的内皮细胞可以防止 动脉粥样硬化斑块的形成通过控制血管的渗透性和炎症。在血流紊乱和葡萄糖改变的情况下，内皮细胞功能障碍并促进动脉粥样硬化斑块的发展。虽然这两种情况已被单独研究，但改变葡萄糖增加血流紊乱区域动脉粥样硬化斑块发展的机制尚未研究。 我们的研究目标是研究血糖和血流机制的改变如何相互作用，导致糖尿病患者动脉粥样硬化加速。我们以前表明，低和高葡萄糖条件下改变内皮细胞对正常血流的反应方式。在这一建议中，我们的目标是研究低， 高葡萄糖对正常或紊乱血流中内皮细胞的影响。我们假设正常的血流可以保护内皮细胞免受葡萄糖诱导的损伤，但是急性葡萄糖变化会加剧血流紊乱的影响。我们将通过合作教育机会让研究生和本科生参与研究。 项目的成功完成将阐明正常的血流如何保护内皮细胞，而紊乱的血流如何加重细胞损伤。这将提高我们对糖尿病动脉粥样硬化尽管全身葡萄糖变化仍然是一种局灶性疾病的理解。在未来，这将为糖尿病血管疾病创造新的疗法。这也将提高本科机械和生物医学工程学生的研究机会，提供6个月的合作教育职位，在我们的细胞mechanodonduction实验室。这些经验将扩大学生对生物力学研究多样性的认识，同时激励他们探索健康研究事业。

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.