MOLECULAR-BIOLOGY OF ATHEROSCLEROSIS

For much of the last century, the development of arteriosclerosis was regarded as an inevitable degenerative process. Osler stated: ''the st ability 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 va riety of elastic and muscular fibers in the blood vessels, some are un able to resist the wear and tear of daily life'' [1]. Recently, thinki ng regarding atherogenesis has evolved from vague concepts of inevitab le degeneration to a more precise sequence of molecular and cellular e vents. As we enhance our understanding of its fundamental mechanisms, we can begin to approach atherogenesis as a modifiable process. Eventu ally, mastery of the cell and molecular biologies of atherosclerosis m ay permit the development of novel strategies for mitigating this prev alent disease. Atherogenesis in humans generally occurs over many year s, often measured in decades. Lesion initiation may occur as early as childhood. Lesion evolution and growth varies according to heredity, g ender, and well-defined risk factors. Complications of atheroma that u sually underlie the acute manifestations of this disease may come abou t suddenly. Some individuals with atherosclerosis may never have sympt oms, others may have only chronic stable manifestations, and yet other s 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 athe roma. We will discuss aspects of lesion initiation, progression, and c omplication. 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 process es. (C) 1997 Elsevier Science Ireland Ltd.