赤血球膜脂肪酸, 膜流動性および変形能と動脈硬化

Abstract

It is a well-known fact that lipids play a role in the development and progression of atherosclerosis. With the recent refinement of methods for analyzing lipids, attention has been directed to phospholipid fatty acids as additional factors that might also possibly be concerned in this relationship. Worthy of particular note is the rapid progress that has been made in the study of the causal relationship between erythrocyte membrane polyunsaturated fatty acids and the pathogenesis and progression of atherosclerosis. The present study was undertaken to investigate the influences of erythrocyte membrane fatty acids (especially polyunsaturated fatty acids), fluidity and deformability upon the development of atherosclerosis and also to determine if destruction of erythrocytes having an abnormal membrane fatty acid composition (increased phospholipid fatty acid C18=2, decreased C20-4) plays a role as a factor to promote the development of atherosclerosis. Involved in this study were elderly patients, above 65 years of age, with hyperlipidemia (serum total cholesterol≥250mg/dl) but without any other disease than arteriosclerosis and hyperlipidemia, non-hyperlipidemic elderly persons (serum total cholesterol<250mg/dl) and healthy young adults, numbering 35. Immature and senescent erythrocytes from these subjects were determined for the contents of free cholesterol, phospholipids and fatty acids as well as for phospholipid composition and also assessed for membrane fluidity (in terms of an ESR order parameter, S value) and deformability (by nuclepore filtration technique and spleen perfusion method). Erythrocytes from rabbits with hyperlipidemia induced by feeding 1% cholesterol in diet were employed as experimental animals material. The results indicate that senescent erythrocytes of hyperlipidemic elderly patients, when compared with immature erythrocytes from the same subjects, showed the following significant changes in membrane parameters: raised free cholesterol, decreased phospholipids, increased C/P ratio, increased relative proportion of C18=2 and decreased relative proportions of C20=4 and polyunsaturated fatty acids (C>20). Comparisons with senescent erythrocytes from the other 2 groups of subjects also showed a similar trend. Senescent erythrocytes had an increased C/P ratio, gave an increased S value with a spin labelling agent I (5, 10) COOH, and had reduced membrane fluidity as a result of decrease in C20-4 fraction of membrane fatty acid. Erythrocytes of the elderly and hyperlipidemic rabbits, when tested by nuclepore filtration method (pore size: 5μ), were found to have a prolonged passage time (hence diminished deformability) and also showed a marked post-perfusion reduction in population in spleen perfusion test. Senescent erythrocytes having abnormalities in membrane fatty acid, whose number increase with aging, are destroyed in the spleen to liberate lipids into the circulation. By way of lipid-degrading and resynthesizing actions of phospholipase present in the blood, fatty acids are formed and deposited in arterial walls, thereby participating in the genesis of atherosclerosis.In conclusion, from what has been mentioned above it seems warrantable to reason that abnormalities in erythrocyte membrane fatty acids (increased saturated fatty acids and decreased polyunsaturated fatty acids) lead to reduced membrane fluidity with subsequent senscence of membrane and decreased deformability of the cells and these factors are intimately concerned with the pathogenesis and evolution of atherosclerosis.