LCATの血液流動性への関与

Abstract

Blood stasis occurred as the result of sclerotic changes in the arteries accelerates the formation of ischemic lesions with respect to decrease in blood supply to the tissues. The rheological properties of blood and its components play an important role in the physiology of blood flow, and the augmentation of blood fluidity elicited by improvement in the properties of plasma and corpuscular components prevents tissues from thrombotic diseases even in the aged with atherosclerotic changes. The alterations in the structure of the erythrocyte membrane which is mainly composed of lipids and proteins give influence on erythrocyte deformability. Mature erythrocyte is not capable of the de novo synthesis of cholesterol. One of the notable features of blood cholesterol is ability to move between erythrocyte membrane and plasma under regulation by LCAT. This study was intended to clarify the participation of LCAT in blood fluidity disclosed by the measurement of deformability index in connection with the observations of the interaction of lipids between plasma and erythrocyte membrane.Fasting blood specimens were drawn from 24 healthy persons with the age of 20 to 23 years. Deformability index was measured by the method of Reid et al. Erythrocyte membrane was separated by the method of Dodge et al. for the analysis of free cholesterol, phospholipids and total protein. Free cholesterol (FC) and phospholipids (PL) were determined by enzymatic methods, total protein (TP) by Lowry's method. The fractionation of phospholipids was carried out by thin-layer chromatography following the extraction of lipid by Folch's solution. Sum of phosphatidylcholine (PC) and sphingomyeline (SM) in the outer layer, and the value of phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the inner layer of the membrane were calculated. Then, the ratio of PC+SM to PE+PS (PC+SM/PE+PS) was investigated in order to clarify the interactions of lipids in the membrane. LCAT activity was assessed by Nagasaki and Akanuma's method.The properties of blood in subjects were tabulated in Table 1. The ratio of FC to PL (FC/PL) in plasma was directly proportional to LCAT activity, FC/PC in erythrocyte membrane was directly to the ratio in plasma. FC in the membrane was inversely proportional to PC+SM/PE+PS and FC inversely to TP. Deformability index was directly proportional to membrane TP, inversely to TP/FC+PL, and LCAT activity.Results obtained in this study by observations of the influence on deformability index indicated close relations of plasma cholesterol, phospholipids and LCAT to hemorheological behavior. The intimate association of LCAT with blood fluidity was confirmed by direct connection of this enzyme with deformability index in addition to the indirect participation through the effect on FC/PL in plasma which affects the ratio in membrane. Although the important role of LCAT in lipid metabolism has been established, there have been conflicting data dealing with participation of this enzyme in the myocardial infarction which is greatly affected by abnormal lipid metabolism. Some authors have refered to severe atherosclerotic changes in not all familiar LCAT deficiency cases and have illustrated a little association of LCAT with occurrence of atherosclerotis in abnormal lipid metabolism. No articles have been found evidence that contradict the significance of high viscosity and low filtrability observed in blood of patients with myocardial infarction. Therefore results obtained in this study emphasize the necessity of versatile observations from the view point of hemorheology in addition to lipid metabolism for investigation of role of LCAT in atherosclerotic diseases.