Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography.
BACKGROUND
Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in 142 normolipidemic subjects undergoing coronary angiography.


METHODS
Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography.


RESULTS
Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concentration of larger and triglyceride rich particles (VLDL, chylomicrons). Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02).


CONCLUSIONS
Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.
Linsel-Nitschke
Patrick
P
Department of Medicine, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany. p.linsel-nitschke@cardiogenics.eu
Jansen
Henning
H
Aherrarhou
Zouhair
Z
Belz
Stefanie
S
Mayer
Björn
B
Lieb
Wolfgang
W
Huber
Fritz
F
Kremer
Werner
W
Kalbitzer
Hans-Robert
HR
Erdmann
Jeanette
J
Schunkert
Heribert
H
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D003251:Constriction, Pathologic; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood* / Q000145:classification; D053439:Lipoproteins, HDL2 / Q000097:blood; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D012306:Risk
D016632:Apolipoprotein A-I; D008074:Lipoproteins; D053439:Lipoproteins, HDL2; D002784:Cholesterol