Factor VII activation, apolipoprotein A-I and reverse cholesterol transport: possible relevance for postprandial lipaemia.
Postprandial lipaemia is associated with activation of factor VII (FVII) and efflux of cholesterol from tissues to nascent plasma high density lipoproteins (HDL) containing apolipoprotein A-I (apo A-I). To determine whether FVII activation and cholesterol efflux occur together in other situations, the responses to intravenous infusion of HDL-like apo A-I/phosphatidylcholine discs were measured in 10 healthy men. Disc infusion (40 mg apo A-I/kg body weight) over 4 h was followed by increases in HDL cholesteryl ester and plasma apo A-I (p <0.0001). Significant activation of FVII was apparent during infusion in fasting subjects (p = 0.03), activated FVII averaging 123% of baseline value by 12 h (p <0.0001). Plasma thrombin-antithrombin (TAT) complex increased to 156% of baseline level by 12 h (p >0.05) but individual responses differed considerably. Peak TAT post-infusion was associated inversely with peak HDL triglyceride concentration (p = 0.004). The coagulation responses to disc-infusion may be due to transfer of phosphatidylserine to cell surfaces during cholesterol efflux.
Miller
G J
GJ
MRC Epidemiology and Medical Care Unit, Wolfson Institute of Preventive Medicine, London, United Kingdom.
Cooke
C J
CJ
Nanjee
M N
MN
Howarth
D J
DJ
Cooper
J A
JA
Stepanova
I P
IP
Morrissey
J H
JH
Miller
N E
NE
D000328:Adult; D000990:Antithrombin III; D016632:Apolipoprotein A-I / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000097:blood; D004789:Enzyme Activation / Q000187:drug effects; D005167:Factor VII / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology; D007263:Infusions, Parenteral; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000187:drug effects; D008297:Male; D010447:Peptide Hydrolases / Q000097:blood; D010713:Phosphatidylcholines / Q000008:administration & dosage; D019518:Postprandial Period / Q000502:physiology
D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; C059714:HDL cholesteryl ester; D008075:Lipoproteins, HDL; D010713:Phosphatidylcholines; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005167:Factor VII; D002784:Cholesterol; D010447:Peptide Hydrolases