Cause of thrombosis in human atherosclerotic arteries

Abstract

Although it has been known for a long time that thrombosis nearly always develops in atherosclerotic arteries—and almost never in normal vessels—the mechanism through which atherosclerosis promotes thrombosis was unknown until this problem was explored through histologic examination of complete serial section sets of thrombosed atherosclerotic arteries. These studies, repeatedly confirmed, revealed that the thrombi are triggered by microscopic cracks in the collagen cap of advanced plaques. Blood most often seeps from the arterial lumen through the cracks into the underlying lipid gruel before the breaks or cracks are plugged by the thrombi (which function as hemostatic seals of the breaks). These results are parallel to results of experimental studies in which the synergism of endotheliotoxic and pressor agents produced thrombi over cap breaks and sub-break hemorrhages only in arteries with advanced collagen-rich plaques, not in arteries with early atherosclerosis or in normal vessels. This finding indicates that advanced atherosclerosis makes the arterial wall much more fragile and that, once broken, this wall exposes the blood to powerful thrombogenic materials that do not exist in normal arterial tissue. At present, human and experimental evidence suggest that the thrombogenic fissures of advanced plaque caps can be promoted by several factors, such as a surge in intraarterial pressure or insults that damage the caps structurally and increase their vulnerability to any type of stress such as certain metabolic, exogenous chemical and immune insults, spontaneous molecular changes of collagen with time and hemorrhages of capillaries that invade advanced plaques from the adventitia or the arterial lumen.