Libby P, Sukhova G, Lee R T, Liao J K
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Int J Cardiol. 1997 Dec 31;62 Suppl 2:S23-9. doi: 10.1016/s0167-5273(97)00238-6.
For much of the last century, the development of arteriosclerosis was regarded as an inevitable degenerative process. Osler stated: "the stability of tubing of any sort depends on the structure and on the sort of material used; and so it is with the human being. With the poor variety of elastic and muscular fibers in the blood vessels, some are unable to resist the wear and tear of daily life" [1]. Recently, thinking regarding atherogenesis has evolved from vague concepts of inevitable degeneration to a more precise sequence of molecular and cellular events. As we enhance our understanding of its fundamental mechanisms, we can begin to approach atherogenesis as a modifiable process. Eventually, mastery of the cell and molecular biologies of atherosclerosis may permit the development of novel strategies for mitigating this prevalent disease. Atherogenesis in humans generally occurs over many years, often measured in decades. Lesion initiation may occur as early as childhood. Lesion evolution and growth varies according to heredity, gender, and well-defined risk factors. Complications of atheroma that usually underlie the acute manifestations of this disease may come about suddenly. Some individuals with atherosclerosis may never have symptoms, others may have only chronic stable manifestations, and yet others may experience fatal or life-threatening acute events without having passed through a phase of chronic symptoms. This review will consider in turn each of the three major phases in the life history of an atheroma. We will discuss aspects of lesion initiation, progression, and complication. Rather than attempting a comprehensive overview, we will focus primarily on selected examples where new information sheds light on potential molecular mechanisms underlying these pathologic processes.
在上个世纪的大部分时间里，动脉硬化的发展被视为一个不可避免的退行性过程。奥斯勒指出：“任何一种管道的稳定性取决于其结构和所用材料的种类；人类也是如此。血管中弹性纤维和肌纤维种类不佳，一些人无法抵抗日常生活的磨损”[1]。最近，关于动脉粥样硬化发生的认识已从不可避免的退化这一模糊概念演变为更精确的分子和细胞事件序列。随着我们对其基本机制的理解不断加深，我们可以开始将动脉粥样硬化的发生视为一个可改变的过程。最终，掌握动脉粥样硬化的细胞生物学和分子生物学可能会促使开发出减轻这种常见疾病的新策略。人类的动脉粥样硬化发生通常需要很多年，常常以数十年计。病变起始可能早在儿童时期就会出现。病变的演变和发展因遗传、性别以及明确的风险因素而异。动脉粥样硬化的并发症通常是该疾病急性表现的基础，可能会突然发生。一些患有动脉粥样硬化的人可能从未出现症状，另一些人可能只有慢性稳定的表现，还有一些人可能会经历致命或危及生命的急性事件，而没有经历过慢性症状阶段。本综述将依次探讨动脉粥样硬化病程中三个主要阶段的每一个阶段。我们将讨论病变起始、进展和并发症等方面。我们不会试图进行全面概述，而是将主要关注一些特定的例子，在这些例子中，新信息揭示了这些病理过程潜在的分子机制。
