Flow, NO, and atherogenesis

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Abstract
Atherosclerosis is the major cause of death and disability in the United States, Europe, and much of Asia. The lesions of atherosclerosis have a nonuniform distribution in the vasculature and are prone to develop at bends, branches, and bifurcations of the aorta and its conduit arteries. At these sites in the vasculature laminar flow is disturbed by recirculation, which resembles an eddy at a river branch. Here the endothelium of the blood vessel is exposed to reduced and oscillating flow, a hemodynamic condition that produces physicochemical and biological alterations predisposing to atherogenesis (Fig. 1). Recirculation causes an increase in particle residence time, so that lipoproteins and monocytes (the anlagen of atherosclerosis) have greater contact with the endothelium in these regions (1). The endothelium itself is morphologically altered. In relatively straight segments of a conduit vessel, endothelial cells are regularly aligned, each cell with its longitudinal axis oriented in the direction of flow. By contrast, in areas of disturbed flow, the usual orientation of endothelial cells is lost, and the cells become more polygonal in appearance. Intriguingly, endothelial cells at branch points appear to age faster. Endothelial cells exposed to disturbed flow in vitro turn over more rapidly (2). In human iliac arteries, endothelial cells at the bifurcation have shorter telomeres, consistent with a focal acceleration of senescence (3). Senescent human endothelial cells produce less nitric oxide (NO⋅), generate more superoxide anion (O), and are more adhesive for monocytes, effects that can be reversed by transfection with the gene encoding telomerase (4). Vascular effects of laminar or disturbed flow. …
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