Elsayed Essam, Becker Richard C
Department of Medicine, UMass-Memorial Medical Center, Cardiovascular Thrombosis Research Center, University of Massachusetts Medical School, Worcester, MA, USA.
J Thromb Thrombolysis. 2003 Feb;15(1):11-8. doi: 10.1023/a:1026184100030.
Atherosclerotic disease is recognized as a chronic inflammatory disorder with intermittent and widely variable phases of cellular proliferation and heightened thrombotic activity. The multi-tiered links between inflammation, atherogenesis and thrombogenesis provide a unique opportunity for research and development of pharmaceuticals which target one or more critical pathobiologic steps (Fig. 1). The purpose of the following review on heparin compounds is to comprehensively examine the multi-cellular, pleuripotential effects of a commonly used anticoagulant drug in the context of normal and disease-altered vascular responses and illustrate possible constructs for avenues of subsequent investigation in the field of atherothrombosis. The overview is divided into five integrated parts; antiinflammatory properties of the normal vessel wall, the relationship between glycosaminoglycans and inflammation, heparin-mediated effects on cellular inflammatory responses, association between molecular weight and antiinflammatory capabilities, and oral heparin compounds for achieving prolonged cell-based inhibition.
动脉粥样硬化疾病被认为是一种慢性炎症性疾病,具有细胞增殖和血栓形成活性增强的间歇性且广泛变化的阶段。炎症、动脉粥样硬化形成和血栓形成之间的多层联系为针对一个或多个关键病理生物学步骤的药物研发提供了独特的机会(图1)。以下关于肝素化合物的综述目的是在正常和疾病改变的血管反应背景下,全面研究一种常用抗凝药物的多细胞、多潜能效应,并阐述动脉粥样硬化血栓形成领域后续研究可能的构建途径。综述分为五个综合部分:正常血管壁的抗炎特性、糖胺聚糖与炎症的关系、肝素介导的对细胞炎症反应的影响、分子量与抗炎能力的关联以及用于实现基于细胞的长期抑制的口服肝素化合物。