Plasma exchange and low density lipoprotein apheresis in Watanabe heritable hyperlipidemic rabbits.

Abstract

Comparison of the effects of plasma exchange using llpoproteln-deflclent plasma with those of LDL apheresis using a dextran sulphate column was undertaken In two groups of Watanabe heritable hyperlipidemic rabbits pre-labelled with 3 H-cholesterol. Total and HDL cholesterol were reduced more by plasma exchange but HDL cholesterol rebounded higher after LDL apheresis; rises In HDL cholesterol correlated with preceding decreases In both HDL and total cholesterol. An Increase In the specific activity of HDL cholesterol occurred on the day after each procedure, being more marked after plasma exchange, and was accompanied by a decrease In the cholesterol/phosphollpld ratio of HDL. These results suggest that an Influx of extravascular HDL Into plasma occurred after both procedures, resulting In mobilization of tissue cholesterol. (Arteriosclerosis 7:256-261, May/June 1987) P lasma exchange, which was first introduced over 10 years ago to treat homozygous familial hypercholesterolemia (FH), results in gradual regression of cutaneous and tendon xanthomata.12 Indirect evidence that this reflects mobilization of tissue cholesterol was obtained by pre-labelling patients' tissues with radioactive cholesterol and demonstrating acute rises in the specific activity of plasma cholesterol after plasma exchange.1 In one instance analysis of individual lipoproteins showed this rise to be localized to high density lipoprotein (HDL) cholesterol. 3 An Inverse relationship between the concentrations of HDL cholesterol in plasma and the size of the exchangeable pool(s) of tissue cholesterol has been proposed 4 and the possible role of HDL in transporting cholesterol from tissues into plasma was reviewed recently.5 Several, 6 " 8 but not all, 9 epidemiological surveys have shown an increased risk of developing coronary heart disease (CHD) in those with low HDL cholesterol levels, and angiographic data suggest that HDL cholesterol is inversely correlated with the severity of coronary arterial lesions, 10 ' 11 as well as with the likelihood that these will progress. 12 -13 In the light of these findings and because plasma exchange removes HDL as well as low density lipoprotein (LDL), techniques designed to conserve HDL during LDL removal have been developed. These include exposing whole blood to heparin-agarose beads 14 removes LDL but not HDL, a process known collectively as LDL apheresis. The present study compares the effects of plasma exchange and LDL apheresis in Watanabe heritable hyperiipldemic (WHHL) rabbits, an animal model of FH.

Role of Monocyte Colony-Stimulating Factor in Foam Cell Generation

“…Four rabbits received an intravenous injection of 3H-cholesterol ( 150 pCi) which was first dissolved in ethanol, then mixed with 2 ml of autologous plasma 1 month before starting M-CSF treatment (32). Four rabbits received an intravenous injection of 3H-cholesterol ( 150 pCi) which was first dissolved in ethanol, then mixed with 2 ml of autologous plasma 1 month before starting M-CSF treatment (32).…”

“…Kano et al (32) reported that specific activities in tissues other than brain and arteries will be higher than that in plasma or HDL by waiting long enough (more than 2 1 days) after the injection of 3H-cholesterol. Kano et al (32) reported that specific activities in tissues other than brain and arteries will be higher than that in plasma or HDL by waiting long enough (more than 2 1 days) after the injection of 3H-cholesterol.…”

Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

“…Each animal group consisted of five rabbits from five litters. Before starting the experiment, and 2 and 6 mo after starting the experiment, 2 ml of blood was taken to measure plasma cholesterol (20), triglyceride levels by enzymatic methods (21), and HDL-cholesterol level by precipitation method (22), one day after apo E injection. After 8.5 mo of the experiment, 5 ml of blood was drawn to evaluate blood cell counts, liver functions, kidney functions, and plasma lipid levels.…”

The scientific basis and future of lipoprotein apheresis

“…This increases the amount of cholesterol transferred to the intermediate and slowly exchangeable pools, manifested clinically by the appearance of numerous cutaneous xanthomas in childhood and later by large tendon xanthomas and severe aortic root atheroma. Lipoprotein apheresis decreases the size of the rapidly exchangeable pool of cholesterol and thereby reduces the influx of cholesterol into the intermediate and slowly exchangeable pools and promotes high‐density lipoprotein (HDL)‐mediated efflux of cholesterol from these pools into plasma [7], resulting in regression of xanthomas and atherosclerotic coronary lesions. In addition to these effects on cholesterol metabolism, apheresis exerts other potentially anti‐atherosclerotic actions resulting from its removal from plasma of proprotein convertase subtilisin/kexin type 9 (PCSK9) [8] and of coagulation factors such as fibrinogen and of proinflammatory cytokines, all of which may play a significant role in the progression of atherosclerosis [9].…”