血小板と動脈硬化のInitiation

Abstract

There are many theories concerned with the pathogenesis of atherosclerosis. The Response-to-Injury Hypothesis is one of them. We have also considered that the endothelial damage with or without thrombi plays an important role in the initiation of atherosclerosis. There have been reported many factors which injure the intima morphologically or functionally. Platelets or aggregated platelets are also considered to be one of the factors. Arachidonic acid production is considered to be an important factor in the mechanism of endothelial injury, because of its detergent action and the strong vasoconstrictive function of its further metabolized material, thromboxane A2 or entoperoxides. We attempted to clarify the direct effect of arachidonic acid on the endothelium.In the experiment I, the arachidonic acid was injected into the aorta via the tubing inserted via the left femoral artery by one shot (1mg/kg) or by snatches (four times, 0.5mg/kg each). Twenty minutes after the injection, the rabbits were sacrificed and the right femoral arteries were fixed by perfusion fixation. The dissected femoral arteries were examined by scanning and transmission electron microscope. In the experiment II, the endothelium of the thoracic and upper part of abdominal aorta was denuded by Fogarty balloon catheter inserted via the left femoral artery, and the abdominal aorta and right femoral artery were examined by scanning electron microscope.In the experiment I, the rabbits in which the arachidonic acid was injected by one shot showed no appreciable pathological change in the endothelium of the right femoral arteries besides vacuolar formation in the cytoplasm in part. The rabbits in which the arachidonic acid was injected by snatches showed various degrees of damage, shrinkage, elevation and/or vacuolation of the cytoplasm, rupture of the cytoplasmic membrane, and denudation of the endothelium only in part without platelet adhesion. In the experiment II, area of the endothelial denudation by catheter showed diffuse platelet adhesion, but no endothelial damage was observed in the right femoral artery.From these experiment, intimal changes produced by aggregated platelets or other stimuli even if the drastic amount of arachidonic acid was administered by one shot was considered to be a minute one. Dysfunction of endothelial cells and the morphological damage initiating atherosclerosis are considered to be produced by repetition of minute stimuli in vivo.