Atherosclerosis and its devastating clinical complications -- arterial thrombosis, ischemia and infarction of the heart, brain and other vital organs, ruptured aortic aneurysms and peripheral vascular insufficiency -- continue to account for the majority of the morbidity and mortality in the adult populations of industrialized nations. Atherosclerosis is a progressive multifactorial process characterized initially by the subendothelial intimal accumulation of lipid-rich macrophages and T lymphocytes ("fatty streaks"), followed by lesions composed of layers of foam cells and proliferating smooth muscle cells with deposition of extracellular matrix ("atheroma"). The disease focally affects the aorta, carotid, coronary, iliac and femoral arteries. Cardio-vascular risk factors include features related to life-style, such as cigarette smoking and obesity, as well as intrinsic factors such as hypertension, hypercholesterolemia and diabetes, which contribute to the pathological mechanisms that make the vascular endothelium dysfunctional, thereby inducing the early processes of atherosclerosis. However, since these factors affect the entire vascular system, they are unlikely to determine alone the focal nature of atherosclerosis. In contrast, the hemodynamic forces imposed on the vascular wall by pulsatile blood flow vary locally, depending on the arterial geometry and architecture and, therefore, are likely candidates for localized alterations. Indeed, evidence accumulates that the localization of atherosclerotic plaques correlates with areas of low and/or oscillating fluid wall shear stress. Moreover, differences in cellular composition between upstream and downstream parts of plaques have been observed, which might refer to a role for arterial flow in the distribution of different cell types. During the last decade, hemodynamics are increasingly recognized as another component playing an important role in the pathophysiology of atherosclerosis.

Nephrology