Molecular biology of atherosclerosis

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.