Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity

doi:10.1194/jlr.M800196-JLR200

HOME

HELP

FEEDBACK

SUBSCRIPTIONS

Serum, but not monocyte macrophage foam cells derived from low HDL-C subjects, displays reduced cholesterol efflux capacity

Shuhei Nakanishi²^,*, Riikka Vikstedt²^,, Sanni Söderlund^*, Miriam Lee-Rueckert, Anne Hiukka^*, Christian Ehnholm, Mikko Muilu, Jari Metso, Jussi Naukkarinen, Leena Palotie, Petri T. Kovanen, Matti Jauhiainen and Marja-Riitta Taskinen¹^,*

^* Division of Cardiology, Department of Medicine, University of Helsinki, Helsinki, Finland
National Public Health Institute and Institute for Molecular Medicine Finland, Helsinki, Finland
Wihuri Research Institute, Kalliolinnantie 4, Helsinki, Finland
^² S. Nakanishi and R. Vikstedt contributed equally to this work.

This work was supported by the Sigrid Juselius Foundation (M-R.T.and M.J.); Research Council for Health, Academy of Finland,Grant 114484 (M.J.); Finnish Foundation for Cardiovascular Research(M-R.T., M.J., and C.E.); Alumni Association for Hiroshima UniversityGraduate School of Biomedical Science, Department of Molecularand Internal Medicine (S.N.); National Graduate School of ClinicalInvestigation (S.S.); Finnish Government scholarship (S.N.);the Aarne Koskelo Foundation (S.N. and S.S.); the Paavo NurmiFoundation (S.N.); the Helsinki University Central HospitalResearch Foundation (M-R.T. and S.S.); Orion Pharma (S.S.);AstraZeneca (S.S.); The Finnish Medical Society Duodecim (S.S.);Finska Läkaresällskapet (R.V.);and the Jenny and AnttiWihuri Foundation (R.V.). Wihuri Research Institute is maintainedby the Jenny and Antti Wihuri Foundation.

Published, JLR Papers in Press, September 11, 2008.

^¹ To whom correspondence should be addressed. Helsinki University Central Hospital, Biomedicum, Haartmaninkatu 8, PO Box 700, FIN-00029, Helsinki, Finland. e-mail: marja-riitta.taskinen{at}helsinki.fi

The main antiatherogenic function of HDL is to promote the effluxof cholesterol from peripheral cells and transport it to theliver for excretion in a process termed reverse cholesteroltransport. The aim of this study was to evaluate the cholesterolefflux capacity in low- and high-HDL subjects by utilizing monocytesand serum from 18 low-HDL and 15 high-HDL subjects. Low andhigh HDL levels were defined, respectively, as HDL $≤$ 10^th andHDL $≥$ 90^th Finnish age/sex-specific percentile. Cholesterol effluxfrom [³H]cholesterol-oleate-acetyl-LDL-loaded monocyte-derivedmacrophages to standard apolipoprotein A-I (apoA-I), HDL₂, andserum was measured. In addition, cholesterol efflux from acetyl-LDL-loadedhuman THP-1 macrophages to individual sera (0.5%) derived fromthe study subjects was evaluated. Cholesterol efflux to apoA-I,HDL₂, and serum from macrophage foam cells derived from low-and high-HDL subjects was similar. The relative ABCA1 and ABCG1mRNA expression levels in unloaded macrophages, as well as theirprotein levels in loaded macrophage foam cells, were similarin the two study groups. Cholesterol efflux from THP-1 foamcells to serum recovered from high-HDL subjects was slightlyhigher than that to serum from low-HDL subjects (P = 0.046).Cholesterol efflux from THP-1 macrophages to serum from studysubjects correlated with serum apoB (P = 0.033), apoA-I (P =0.004), apoA-II (P < 0.0001), and the percentage of apoA-Ipresent in the form of preβ-HDL (P = 0.0001). Our datareveal that macrophages isolated from either low- or high-HDLsubjects display similar cholesterol efflux capacity to exogenousacceptors. However, sera from low-HDL subjects have poorer cholesterolacceptor ability as compared with sera from high-HDL subjects.

Supplementary key words atherosclerosis • reverse cholesterol transport • lipoproteins

Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?