Fay William P, Garg Nadish, Sunkar Madhavi
Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Arterioscler Thromb Vasc Biol. 2007 Jun;27(6):1231-7. doi: 10.1161/ATVBAHA.107.140046. Epub 2007 Mar 22.
The plasminogen activator (PA) system, which controls the formation and activity of plasmin, plays a key role in modulating hemostasis, thrombosis, and several other biological processes. While a great deal is known about the function of the PA system, it remains a focus of intensive investigation, and the list of biological pathways and human diseases that are modulated by normal and pathologic function of its components continues to lengthen. Because of remarkable advances in molecular genetics, the laboratory mouse has become the most useful animal system to study the normal and pathologic functions of the PA system. The purpose of this review is to summarize studies that have used genetically modified mice to examine the functions of the PA system in hemostasis and thrombosis, intimal hyperplasia after vascular injury, and atherosclerosis. Particular emphasis is placed on the vascular functions of PA inhibitor-1, a key regulator of the PA system, and the multiple variables that appear to account for the complex role of PA inhibitor-1 in regulating vascular remodeling. Lastly, the strengths and limitations of using mice to model human vascular disease processes are discussed.
纤溶酶原激活物（PA）系统控制着纤溶酶的形成和活性，在调节止血、血栓形成及其他多种生物学过程中发挥着关键作用。尽管人们对PA系统的功能已有很多了解，但它仍是深入研究的焦点，其组成成分的正常和病理功能所调节的生物学途径及人类疾病的清单仍在不断增加。由于分子遗传学的显著进展，实验室小鼠已成为研究PA系统正常和病理功能最有用的动物模型。本综述的目的是总结那些利用基因工程小鼠来研究PA系统在止血和血栓形成、血管损伤后内膜增生以及动脉粥样硬化中功能的研究。特别强调了PA系统的关键调节因子PA抑制剂-1的血管功能，以及似乎可解释PA抑制剂-1在调节血管重塑中复杂作用的多个变量。最后，讨论了使用小鼠模拟人类血管疾病过程的优点和局限性。
