Atherosclerosis and the vascular biology of aging

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Abstract
With advancing age, a series of structural, architectural and compositional modifications take place in the vasculature. The diameter of the vessels tends to increase, and thickening of intimal and medial layers is often observed. In the subendothelial space, blood-derived leukocytes and an increased amount of “activated” smooth muscle cells are present. Extracellular matrix accumulates and becomes particularly rich in glycosaminoglycans. Collagen content increases, while elastin fibers appear progressively disorganized, thinner, and frequently fragmented. These changes in the normal architecture of the vessel wall, that could be referred to as “the vasculopa-thy of aging”, are likely to be the consequence of adaptive mechanisms to maintain normal conditions of flow, mechanical stress and/or wall tension. Although many of these features are similar to the histological findings of the atherosclerotic vessels, atherosclerosis and age-related “vasculopathy” are two distinct phenomena. Nonetheless, several experimental observations in animal models suggest a special link between “the vascu-lopathy of aging” and atherosclerotic disease, and suggest a particular predisposition of the old vessel to develop the atherosclerotic lesion. Compared to vessels from young animals, older ones show a greater reactivity to mechanical injury and to chronic insults. This may reflect changes in the biology of the vessels that are “intrinsic” to the aging process. Indeed, aging affects the function and responsiveness of the endothelium and vascular smooth muscle cells. Endothelial permeability is increased with age, while ability to produce vasoactive substances declines. Smooth muscle cells from old individuals show a growth advantage over the young ones, and display an increased ability to migrate toward chemoattractants. Moreover, the accumulation of advanced glycation end products (AGEs) occurring with aging can trigger a series of cellular events, such as cellular oxidative stress, expression of leukocyte adhesion molecules, endothelial transmigration of monocytes, and smooth muscle cell chemotaxis, all considered important prelesional events in the atherogenesis process. Taken together, the changes occurring with aging, while unproven to initiate lesion formation per se, are likely to accelerate the development of the atherosclerotic plaque and contribute to increased severity of this disease in the elderly.