HDL and apolipoprotein A1 (apo A1). Their effects on retardation of lipid deposition in aortic intima.

The aim of this study is to clarify whether apo A1 displays a similar role as that of HDL in preventing the development of experimental atherosclerosis. Results were obtained from 4 groups of experiments. (1) Result from 4 successive experiments of tree shrews indicated that high serum HDL level is the main factor in preventing the development of experimental atherosclerosis; (2) Results from 4 successive experiments in rabbits showed that both HDL and apo A1 were able to decrease the extent of lipid deposition and atheromatous lesion developed in the aortic intima; (3) Apo A1 also inhibited the number of monocytes/macrophages infiltrated in aortic intima at the initial stage of fatty streak formation; (4) Similar as HDL, apo A1 phospholipid liposomes promoted markedly the clearance ability of smooth muscle cells on intracellular cholesterol. Conclusively, apo A1 is effective in preventing the development of experimental atherosclerosis. Further study, however, is required to detect an ideal combination of apo A1 with other component, e.g., phospholipid.

High density lipoproteins and prevention of experimental atherosclerosis with special reference to tree shrews.

According to data obtained from epidemiological and experimental survey, serum HDL level is known to be correlated conversely with the incidence of atherosclerosis. Experimental data collected in this article explained part of its mechanism, which is described in four parts as follows: 1. The result of 3 successive experiments on experimental atherosclerosis in tree shrews (total of 96 animals available including 40 as the controls) showed that the serum HDL level had been kept persistantly to 69-88% of the total serum lipoproteins even after a high cholesterol intake for 32 weeks. The incidence of atheromatous lesions developed was only 0-9%, but the incidence of gall stone was very high, 48-84% by gross examination by the end of these experiments. 2. HDL are also capable of (1) promotion of monocyte migration activity; (2) enhancement of cholesterol clearance rate of aortic smooth muscle cells originally isolated from either rabbits or tree shrews; (3) inhibition of 20% of LDL degradation but with no inhibitory effect obtained on Ac-LDL degradation in the endothelial cells; (4) presence of specific binding sites for apo E free HDL on the surface of aortic smooth muscle cells from either rabbits or tree shrews which recognizes apo A1 as a ligand. 3. Data from 2 successive experiments in rabbits showed that HDL lipoproteins (mainly apo A1) possess an inhibitory effect on the development of atheromatous plaques, but not a very strong one. 4. The colesterol clearance effect of smooth muscle cells was markedly enhanced by apo A1/phospholipid liposomes (the apo A1 used was isolated from either rabbit's or tree shrew's serum) in vitro.

[The inhibitory effect of apolipoproteins in HDL on experimental atherosclerosis in rabbits].

The main apolipoproteins in HDL are known to be apo A1, A2, and A4. Apolipoprotein (mainly apo A1) were isolated and purified from about 100 liters of rabbit's serum for the purpose of studying their inhibitory effect on the development of atheromatous plaques in rabbits. Data indicated that lipid content in aortic intima: lipid deposition in intima morphologically; area of atheromatous lesion involved and the severity of atheromatous lesions obtained were much lower in animals of the experimental group after intravenous administration of apolipoproteins isolated from HDL for 8 to 12 weeks than those in animals of the cholesterol control groups in two successive experiments. In accordance with data obtained from epidemiological and experimental surveys. HDL level was known to be correlated reversely with the incidence of atherosclerosis. Data of these experiments confirmed that apolipoproteins (mainly apoA1) in HDL are the main factors of this inhibitory effect. This result provides a scientific basis for the measurement of preparation of certain apolipoproteins (apo A1 and possibly A1) by high bio-technology for prevention and treatment of atherosclerosis in the near future.