Plasma kinetics of a chylomicron-like emulsion in patients with coronary artery disease.
Chylomicron catabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. In rats, triglyceride-rich emulsions can mimic chylomicron metabolism. To further validate this model in man, the emulsion was injected intravenously into fasting and into subjects previously fed a test fatty meal. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined. The fractional clearance rate (FCR) of both labels was markedly reduced in the fed subjects (triglycerides: fed = 0.018 +/- 0.007; fasting = 0.105 +/- 0.013 min-1, P < 0.001; cholesteryl ester: fed = 0.016 +/- 0.001; fasting = 0.040 +/- 0.006 min-1; P < 0.05) indicating that the emulsion and chylomicrons generated from the testinal lipid absorption compete for the same catabolic processes, confirming the validity of the method. The emulsion was injected into 11 patients with CAD and into 11 controls. All had plasma cholesterol < 240 and triglycerides < 250 mg/dl. FCR of triglycerides was 5-fold smaller in CAD compared to controls (0.028 +/- 0.004 and 0.141 +/- 0.069 min-1, respectively, P < 0.01). FCR of cholesteryl ester was 4-fold smaller in CAD than in controls (0.015 +/- 0.004 and 0.056 +/- 0.067 min-1 respectively, P < 0.05). These results indicate that both chylomicron lipolysis and remnant removal are diminished in CAD.
Maranhão
R C
RC
Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil.
Feres
M C
MC
Martins
M T
MT
Mesquita
C H
CH
Toffoletto
O
O
Vinagre
C G
CG
Gianinni
S D
SD
Pileggi
F
F
D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000097:blood; D002784:Cholesterol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002914:Chylomicrons / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000150:complications; D004041:Dietary Fats / Q000493:pharmacokinetics; D004198:Disease Susceptibility; D004347:Drug Interactions; D004655:Emulsions; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood*; D014304:Triolein / Q000008:administration & dosage / Q000493:pharmacokinetics*
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D002914:Chylomicrons; D004041:Dietary Fats; D004655:Emulsions; D006023:Glycoproteins; D008074:Lipoproteins; D010713:Phosphatidylcholines; D014280:Triglycerides; D014304:Triolein; C014409:cholesteryl oleate; D002784:Cholesterol