Soufi Muhidien, Sattler Alexander M, Maisch Bernhard, Schaefer Jürgen R
Department of Internal Medicine, Philipps-University Marburg, Germany.
Herz. 2002 Nov;27(7):637-48. doi: 10.1007/s00059-002-2431-2.
Research in atherosclerosis is a good example how helpful different disciplines such as clinicians, epidemiologists and basic science can collaborate. In recent years our knowledge on cellular and subcellular mechanisms involved in initiation and progress of atherosclerosis has expanded due to the shared knowledge of different disciplines and thanks to new technologies in molecular biology.
The understanding of the molecular basis of inborn errors of LDL metabolism - such as familial hypercholesterolemia due to a defect of the LDL receptor - provided us new insights in physiology and pathophysiology of LDL metabolism. Most recently we have learned much about the vasoprotective HDL cholesterol. HDL is the major player in reverse cholesterol transport and some of its receptors such as ABCA1 and SR-BI were identified. This knowledge gives us a deeper understanding of the complex system which performs reverse cholesterol transport from peripheral tissue and the vessel wall back to the liver.
Furthermore the process of formation and progression of the atherosclerotic plaque has been the focus of recent research. The stability or instability of plaques is depending on the complex interaction of adhesion molecules, monocytes, macrophages, endothelial cells, cytokines, transmitters and proteinases. Since we are unable to prevent plaque formation completely, the stabilization of plaques is a major goal for the coming years. Despite some success (such as the use of statines and ACE inhibitors) there is still a long way to go.
动脉粥样硬化的研究是一个很好的例子，展示了临床医生、流行病学家和基础科学等不同学科如何进行有益的合作。近年来，由于不同学科的知识共享以及分子生物学新技术的出现，我们对动脉粥样硬化发生和发展过程中涉及的细胞和亚细胞机制的认识有所扩展。
低密度脂蛋白（LDL）和高密度脂蛋白（HDL）代谢的病理生理学：对LDL代谢先天性缺陷的分子基础的理解——例如由于LDL受体缺陷导致的家族性高胆固醇血症——为我们提供了关于LDL代谢生理和病理生理的新见解。最近，我们对具有血管保护作用的HDL胆固醇有了更多了解。HDL是逆向胆固醇转运的主要参与者，并且已鉴定出其一些受体，如ABCA1和SR-BI。这些知识使我们对从外周组织和血管壁将胆固醇逆向转运回肝脏的复杂系统有了更深入的理解。
此外，动脉粥样硬化斑块的形成和进展过程一直是近期研究的重点。斑块的稳定性或不稳定性取决于黏附分子、单核细胞、巨噬细胞、内皮细胞、细胞因子、递质和蛋白酶之间的复杂相互作用。由于我们无法完全预防斑块形成，因此斑块的稳定化是未来几年的主要目标。尽管取得了一些成功（如使用他汀类药物和血管紧张素转换酶抑制剂），但仍有很长的路要走。
