The effects of intravenous Triton WR-1339 on factor VII coagulant activity and plasma lipoproteins in normocholesterolaemic and hypercholesterolaemic rabbits.
The hypothesis that lipolysis of large lipoproteins by lipoprotein lipase (LPL) has an important influence on the activation of the contact system of coagulation and subsequently on factor VII activation was tested in rabbits rendered hyperlipidaemic by dietary means and/or by injection of Triton WR-1339. The dietary treatment involved a control diet and two isocaloric diets containing either a 0.5% cholesterol or 0.5% cholesterol and 7.5% safflower oil supplement. Other groups of rabbits were given either a standard diet or the standard diet supplemented with 1% cholesterol. All supplemented diets increased many-fold the concentrations of cholesterol associated with the chylomicron, very low-(VLDL), intermediate-(IDL) and low-density (LDL) lipoprotein fractions. Factor VII coagulant activity (FVIIc) increased significantly in all groups of rabbits fed the cholesterol supplement. The intravenous injection of Triton WR-1339 into rabbits fed either the standard or 1% cholesterol-supplemented diet resulted in increases of plasma cholesterol and triglyceride concentrations up to 36-48 h thereafter, followed by decreases up to completion of the experiment at 72 h. Most of these increases in plasma lipids were associated with the chylomicron and VLDL fractions. Following injection of Triton into rabbits fed either the standard or cholesterol-supplemented diet, changes in FVIIc were biphasic with a decrease in activity in the early intervals when rates of accumulation of plasma lipid were constant, and a progressive increase in activity at later intervals when rates of lipid accumulation declined and then reversed.(ABSTRACT TRUNCATED AT 250 WORDS)
MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, Medical College, St Bartholomew's Hospital, London, UK.
K A
KA
Mitropoulos
G J
GJ
Miller
D J
DJ
Howarth
B E
BE
Reeves
J A
JA
Cooper
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D001777:Blood Coagulation; D002784:Cholesterol / Q000008:administration & dosage / Q000633:toxicity; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage / Q000633:toxicity; D004789:Enzyme Activation; D005167:Factor VII / Q000378:metabolism*; D006937:Hypercholesterolemia / Q000097:blood* / Q000139:chemically induced; D007275:Injections, Intravenous; D008066:Lipolysis / Q000187:drug effects*; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors*; D008074:Lipoproteins / Q000097:blood*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D012450:Safflower Oil / Q000008:administration & dosage / Q000633:toxicity; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013925:Thromboplastin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D000941:Antigens; D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D002914:Chylomicrons; D004041:Dietary Fats; D008074:Lipoproteins; D013501:Surface-Active Agents; D014280:Triglycerides; C042580:factor VII clotting antigen; D011092:Polyethylene Glycols; D012450:Safflower Oil; D005167:Factor VII; D013925:Thromboplastin; D002784:Cholesterol; D008071:Lipoprotein Lipase; C016811:tyloxapol