title: Serum cholesterol efflux potential is an independent predictor of coronary artery atherosclerosis.
abstract: The efflux of cholesterol from cells and its incorporation into HDL is believed to be the initial step in reverse cholesterol transport. This report addresses the question of whether there is a relationship between the ability of serum to promote efflux of cholesterol from cells in culture and the severity of coronary artery atherosclerosis (CAA). Surgically postmenopausal cynomolgus monkeys (n=142) were treated for 2-years with conjugated equine estrogens (CEE), CEE plus medroxyprogesterone acetate, or two different doses of tibolone, a synthetic steroid. CAA was determined at necropsy, and the cholesterol efflux potential of serum from each animal was determined using 3H-cholesterol-labeled Fu5AH cells and human skin fibroblasts in culture. A significant negative correlation was seen between CAA and cholesterol efflux from Fu5AH cells (r=-0.44, P< or =0.0001), but not skin fibroblasts. Although there was a wide range of plasma HDL cholesterol concentrations in these animals (10-81 mg/dl), using multiple regression analysis, LDL+VLDL cholesterol and the serum cholesterol efflux potential were the only significant independent predictors of CAA, explaining 41.6 and 10.7% of the variability (P<0.0001), respectively. Thus, the potential of serum to promote cholesterol efflux from Fu5AH cells may represent a useful independent measure for improving the assessment of CAA risk.
authors.affiliation: Comparative Medicine Clinical Research Center, Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. tomi.mikkola@hus.fi
authors.forename: Tomi S
authors.initials: TS
authors.lastname: Mikkola
authors.forename: Mary S
authors.initials: MS
authors.lastname: Anthony
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Clarkson
authors.forename: Richard W
authors.initials: RW
authors.lastname: St Clair
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood / Q000187:drug effects; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood / Q000187:drug effects; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D015243:Cholesterol, VLDL / Q000097:blood / Q000187:drug effects; D003324:Coronary Artery Disease / Q000097:blood*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020847:Estrogen Receptor Modulators / Q000008:administration & dosage; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D000882:Haplorhini; D008955:Models, Cardiovascular; D015999:Multivariate Analysis; D009652:Norpregnenes / Q000008:administration & dosage; D015588:Observer Variation; D011237:Predictive Value of Tests; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013223:Statistics as Topic; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016387:Women's Health
chemical_list: D016632:Apolipoprotein A-I; D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D020847:Estrogen Receptor Modulators; D009652:Norpregnenes; D002784:Cholesterol; C027385:tibolone