Atherosclerosis: Lipoproteins, cell biology and vascular physiology

动脉粥样硬化：脂蛋白、细胞生物学和血管生理学

• 批准号: nhmrc : 482800
• 负责人: Prof David Celermajer
• 金额: $ 697.58万
• 依托单位: The Heart Research Institute
• 依托单位国家: 澳大利亚
• 项目类别: Programs
• 财政年份: 2008
• 资助国家: 澳大利亚
• 起止时间: 2008-01-01 至 2012-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/atherosclerosis-lipoproteins-cell-vascular-physiology/94965
• 关键词: Atherosclerosis; Lipoproteins; cell; biology; vascular

The world is confronting a major new epidemic of premature heart disease that is being driven by a global increase in obesity. There are several factors that contribute to the increased risk of heart disease in overweight and obese people. One is a low blood level of the “good” HDL cholesterol that normally protects against heart disease. Another relates to a decreased ability to remove cholesterol from the walls of arteries where it builds up to cause heart disease. A third is the fact that obesity is associated with a state of chronic inflammation of the blood vessels. This inflammation not only accelerates the development of heart disease but also makes people who have cholesterol accumulated in their arteries more likely to actually have a heart attack. And a fourth is the fact that the lining of blood vessels does not function normally in overweight and obese people. This loss of normal function is a very early sign of future heart disease. These factors are closely inter-related, with the “good” HDL playing a central role in removing cholesterol from arteries, inhibiting arterial inflammation and promoting normal function and repair of the lining of blood vessels. HDL is complex, consisting of a mixture of several subpopulations of particles that vary in shape, size and composition. Furthermore, these HDL subpopulations are continually remodelled as they circulate in blood in reactions promoted by a number of blood factors that change their size and composition. A major component of the research to be conducted in this program relates to understanding how the HDL subpopulations in human blood are regulated and how they protect against heart disease. The applicants have already made major contributions to understanding the functions of the “good” HDLs, how they take cholesterol out of cells in the artery wall, how they inhibit inflammation of the arteries and how they improve the function of the artery lining. We propose to extend these studies to establish how these protective functions can be enhanced, to find out which of the HDL subpopulations are most protective, and to identify how to increase the most protective HDLs in people at risk of heart disease.

世界正面临着一种新的主要流行病，即由全球肥胖症增加引起的早发性心脏病。有几个因素导致超重和肥胖人群患心脏病的风险增加。一个是血液中“好”的高密度脂蛋白胆固醇水平低，而高密度脂蛋白胆固醇通常可以预防心脏病。另一个与降低从动脉壁清除胆固醇的能力有关，胆固醇在动脉壁积聚导致心脏病。第三个是肥胖与血管慢性炎症有关。这种炎症不仅会加速心脏病的发展，而且会使动脉中胆固醇积累的人更容易患心脏病。第四个是超重和肥胖的人的血管内膜功能不正常。这种正常功能的丧失是未来心脏病的早期征兆。这些因素密切相关，“好”HDL在清除动脉中的胆固醇，抑制动脉炎症，促进血管内膜的正常功能和修复方面发挥着核心作用。HDL是复杂的，由形状、大小和组成不同的几个颗粒亚群的混合物组成。此外，这些HDL亚群在血液中循环时不断重塑，这些反应由许多改变其大小和组成的血液因子促进。该计划中进行的研究的一个主要组成部分涉及了解人类血液中HDL亚群是如何调节的，以及它们如何预防心脏病。申请人已经为理解“好”HDL的功能做出了重大贡献，它们如何将胆固醇从动脉壁细胞中取出，如何抑制动脉炎症以及如何改善动脉内膜的功能。我们建议扩展这些研究，以确定如何增强这些保护功能，找出哪些HDL亚群最具保护性，并确定如何增加心脏病风险人群中最具保护性的HDL。