Lord Susan T
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Curr Opin Hematol. 2007 May;14(3):236-41. doi: 10.1097/MOH.0b013e3280dce58c.
Elevated fibrinogen is a cardiovascular risk factor. Recent work provides a rationale for this risk, as abnormal fibrin clot structure, strength and stability correlates with coronary artery disease. This review describes in-vitro experiments whose intent is to define the molecular mechanisms that control clot architecture and function in vivo.
Biochemical and structural data continue to define the interactions between monomer units that assemble into a fibrin clot. In particular, 'A: a' interactions dominate the first step in fiber formation, while the analogous 'B: b' interactions have a minor role. Studies show the N-terminus of Bbeta, the C-terminus of Aalpha, and the splice variant gamma' modulate fibrin clot structure. Measurement of the mechanical properties of fibrinogen and fibrin show fibrin fibers are among the strongest in nature. Studies have identified fibrinogen-binding proteins that influence clot structure and function.
These findings defined mechanisms that control fibrin clot structure, strength and stability. This basic information provides direction for clinical studies to examine clot properties in pathologic thrombosis and pharmaceutical studies to develop therapeutic interventions to prevent or control cardiovascular disease. These studies also establish novel techniques to examine individual bonds, molecules and fibers.
纤维蛋白原升高是一种心血管危险因素。近期研究为这种风险提供了理论依据，因为异常的纤维蛋白凝块结构、强度和稳定性与冠状动脉疾病相关。本综述描述了旨在确定体内控制凝块结构和功能的分子机制的体外实验。
生化和结构数据继续阐明组装成纤维蛋白凝块的单体单元之间的相互作用。特别是，“A:a”相互作用在纤维形成的第一步中占主导地位，而类似的“B:b”相互作用作用较小。研究表明，Bβ的N端、Aα的C端和剪接变体γ'调节纤维蛋白凝块结构。对纤维蛋白原和纤维蛋白力学性能的测量表明，纤维蛋白纤维是自然界中最强的纤维之一。研究已经确定了影响凝块结构和功能的纤维蛋白原结合蛋白。
这些发现确定了控制纤维蛋白凝块结构、强度和稳定性的机制。这些基础信息为临床研究检查病理性血栓形成中的凝块特性以及药物研究开发预防或控制心血管疾病的治疗干预措施提供了方向。这些研究还建立了检查单个键、分子和纤维的新技术。
