Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice

J Lipid Res. 2015 Jul;56(7):1282-95. doi: 10.1194/jlr.M048629. Epub 2015 May 11.


LCAT, a plasma enzyme that esterifies cholesterol, has been proposed to play an antiatherogenic role, but animal and epidemiologic studies have yielded conflicting results. To gain insight into LCAT and the role of free cholesterol (FC) in atherosclerosis, we examined the effect of LCAT over- and underexpression in diet-induced atherosclerosis in scavenger receptor class B member I-deficient [Scarab(-/-)] mice, which have a secondary defect in cholesterol esterification. Scarab(-/-)×LCAT-null [Lcat(-/-)] mice had a decrease in HDL-cholesterol and a high plasma ratio of FC/total cholesterol (TC) (0.88 ± 0.033) and a marked increase in VLDL-cholesterol (VLDL-C) on a high-fat diet. Scarab(-/-)×LCAT-transgenic (Tg) mice had lower levels of VLDL-C and a normal plasma FC/TC ratio (0.28 ± 0.005). Plasma from Scarab(-/-)×LCAT-Tg mice also showed an increase in cholesterol esterification during in vitro cholesterol efflux, but increased esterification did not appear to affect the overall rate of cholesterol efflux or hepatic uptake of cholesterol. Scarab(-/-)×LCAT-Tg mice also displayed a 51% decrease in aortic sinus atherosclerosis compared with Scarab(-/-) mice (P < 0.05). In summary, we demonstrate that increased cholesterol esterification by LCAT is atheroprotective, most likely through its ability to increase HDL levels and decrease pro-atherogenic apoB-containing lipoprotein particles.

Keywords: knockout; lecithin:cholesterol acyltransferase; scavenger receptor class B member I.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Atherosclerosis / blood*
  • Atherosclerosis / enzymology*
  • Atherosclerosis / etiology
  • Atherosclerosis / metabolism
  • Biological Transport
  • Blood Platelets / metabolism
  • Blood Platelets / pathology
  • CD36 Antigens / deficiency*
  • CD36 Antigens / genetics*
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Diet, High-Fat / adverse effects*
  • Erythrocyte Count
  • Erythrocytes / metabolism
  • Erythrocytes / pathology
  • Esterification
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Knockout Techniques
  • Humans
  • Lipoproteins, VLDL / biosynthesis
  • Lipoproteins, VLDL / blood
  • Lipoproteins, VLDL / chemistry
  • Liver / metabolism
  • Mice
  • Mice, Transgenic
  • Phosphatidylcholine-Sterol O-Acyltransferase / genetics
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism*
  • Platelet Count


  • CD36 Antigens
  • Lipoproteins, VLDL
  • Cholesterol
  • Phosphatidylcholine-Sterol O-Acyltransferase