Research

Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography

Patrick Linsel-Nitschke^1* , Henning Jansen^1* , Zouhair Aherrarhou¹ , Stefanie Belz¹ , Björn Mayer¹ , Wolfgang Lieb¹ , Fritz Huber^2,3 , Werner Kremer² , Hans-Robert Kalbitzer² , Jeanette Erdmann¹ and Heribert Schunkert¹

¹  Department of Medicine, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

²  Biophysics Institute, University of Regensburg, Josef Engert Strasse 9, 93053 Regensburg, Germany

³  LipoFIT Analytics GmbH, Josef Engert Strasse 9, 93053 Regensburg, Germany

author email corresponding author email* Contributed equally

Lipids in Health and Disease 2009, 8:14doi:10.1186/1476-511X-8-14

Published:	6 April 2009

Abstract

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 in142 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 concntration 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).

Conclusion

Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.