Weinberg Peter D
School of Animal and Microbial Sciences, University of Reading, Reading, UK.
J Vasc Res. 2004 Jan-Feb;41(1):1-17. doi: 10.1159/000076124. Epub 2004 Jan 12.
A large number of processes are involved in the pathogenesis of atherosclerosis but it is unclear which of them play a rate-limiting role. One way of resolving this problem is to investigate the highly non-uniform distribution of disease within the arterial system; critical steps in lesion development should be revealed by identifying arterial properties that differ between susceptible and protected sites. Although the localisation of atherosclerotic lesions has been investigated intensively over much of the 20th century, this review argues that the factor determining the distribution of human disease has only recently been identified. Recognition that the distribution changes with age has, for the first time, allowed it to be explained by variation in transport properties of the arterial wall; hitherto, this view could only be applied to experimental atherosclerosis in animals. The newly discovered transport variations which appear to play a critical role in the development of adult disease have underlying mechanisms that differ from those elucidated for the transport variations relevant to experimental atherosclerosis: they depend on endogenous NO synthesis and on blood flow. Manipulation of transport properties might have therapeutic potential.
动脉粥样硬化的发病机制涉及大量过程，但尚不清楚其中哪些过程起限速作用。解决这一问题的一种方法是研究疾病在动脉系统内高度不均匀的分布情况；通过识别易损部位和受保护部位之间不同的动脉特性，应能揭示病变发展的关键步骤。尽管在20世纪的大部分时间里，人们对动脉粥样硬化病变的定位进行了深入研究，但本综述认为，决定人类疾病分布的因素直到最近才被发现。认识到这种分布随年龄变化，首次使得人们能够用动脉壁传输特性的变化来解释它；迄今为止，这种观点仅适用于动物实验性动脉粥样硬化。新发现的传输变化似乎在成人疾病的发展中起关键作用，其潜在机制与已阐明的与实验性动脉粥样硬化相关的传输变化的机制不同：它们依赖于内源性一氧化氮合成和血流。对传输特性的操控可能具有治疗潜力。
