高脂肪食飼育下ウサギの胸部大動脈平滑筋細胞のPGI<sub>2</sub>産生能について

Abstract

Several investigators have reported the decreased PGI2 synthesis by arteries obtained from atherosclerotic animals and patients with atherosclerosis. In contrast to those results, FitzGerald et al, have suggested the increased PGI2 production in atherosclerotic patients in vivo by measuring their increased PGI2-metabolite in urine. On the other hand, the proliferative growth of SMC in intima has been shown to play an important role in the process of atherosclerosis because of its increased capability to produce PGI2.Therefore, we reexamined in vitro PGI2 synthesis by aortic explants of thoracic aorta obtained from atherosclerotic rabbit fed a cholesterol rich diet for 4 months. Aortic explants weighing about 10-20mg were incubated in 1ml of KRB-glucose buffer (pH 7.4), for 30 min at 37°C. Aortic SMC were also obtained from medial explants of normal rabbits (thoracic aorta) and from Intimal explants of atherosclerotic rabbits and then cultured in DME medium supplemented with 10% FCS, routinely. PGI2 levels in incubation media and culture media were determined as 6-keto-PGF1α by RIA after extraction and separation as reported previously.Both basal and arachidonic acid-induced productions of PGI2 by aortic explants from atherosclerotic aorta were significantly higher than those of controls. Furthermore, cultured intimal SMC obtained from atherosclerotic rabbit aorta produced a significantly greater amount of PGI2 than medial SMC from normal rabbit aorta under various conditions examined. Therefore, the present data further suggest that intimal growth of SMC may play a pivotal role in the process of atherosclerosis.