부산대학교 도서관

Since more than 30 years ago, we have reported that experimental atherosclerosis similar to that of human beings was produced in monkeys by Vitamin B6 deprived food. However, as the mechanism of formation of atherosclerotic lesion in pyridoxine deficient monkeys was not obvious, we examined the effect of Vitamin B6 and its antagonists on the cultured endothelial cells from fetal bovine aorta. The patients with homocysteinuria, who lack the activity of cystathionine synthetase which needs Vitamin B6 as a cofactor, have the tendency to suffer from atherosclerosis in their early life. So it has been considered that the impairment of sulfur-containing amino acid metabolism may play a role in the formation of atherosclerosis in monkeys fed on Vitamin B6 deprived food. Because the patients with cystathionine synthetase deficiency had homocysteine in their blood at higher concentrations, we also studied the effect of homocysteine. The cultured smooth muscle cells produce ECM (Extracellular Matrix) and we examined its effect on the growth of endothelial cells.We used isoniazid and deoxypyridoxine as Vitamin B6-antagonists. It was considered that isoniazid had no effect on the growth of endothelial cells at a usual dosage as an antituberculous drug, because the growth of isoniazid group (1mM) was the same as that of the control group. Deoxypyridoxine had suppressed the growth of endothelial cells at concentration 1, 2.5 and 5mM. Pyridoxal phosphate, active form of Vitamin B6, had no effect at lower concentration (0.01mM) but a supressive effect at higher concentrations (0.1mM, 1mM). DL-homocysteine did not suppress the growth of endothelial cells at concentration 0.5, 1 and 2mM. The cell number of DL-homocysteine group is slightly more than that of control group after confluence.The role of Vitamin B6 in the formation of atherosclerosis is not clear in this study using endothelial cells alone in vitro. It was supposed, however, that the atherosclerosis may be caused by multiple factors, for example, not only endothelial cells but also smooth muscle cells, platelets, coagulants and their interactions in vivo. Vitamin B6 depletion may also take part in the formation of atherosclerosis by influencing many factors but many problems regarding these mechanisms still remain to be clarified.