Lecithin:cholesterol acyltransferase deficiency increases atherosclerosis in the low density lipoprotein receptor and apolipoprotein E knockout mice.
The purpose of the present study was to test the hypothesis that lecithin:cholesterol acyltransferase (LCAT) deficiency would accelerate atherosclerosis development in low density lipoprotein (LDL) receptor (LDLr-/-) and apoE (apoE-/-) knockout mice. After 16 weeks of atherogenic diet (0.1% cholesterol, 10% calories from palm oil) consumption, LDLr-/- LCAT-/- double knockout mice, compared with LDLr-/- mice, had similar plasma concentrations of free (FC), esterified (EC), and apoB lipoprotein cholesterol, increased plasma concentrations of phospholipid and triglyceride, decreased HDL cholesterol, and 2-fold more aortic FC (142 +/- 28 versus 61 +/- 20 mg/g protein) and EC (102 +/- 27 versus 61+/- 27 mg/g). ApoE-/- LCAT-/- mice fed the atherogenic diet, compared with apoE-/- mice, had higher concentrations of plasma FC, EC, apoB lipoprotein cholesterol, and phospholipid, and significantly more aortic FC (149 +/- 62 versus 109 +/- 33 mg/g) and EC (101 +/- 23 versus 69 +/- 20 mg/g) than did the apoE-/- mice. LCAT deficiency resulted in a 12-fold increase in the ratio of saturated + monounsaturated to polyunsaturated cholesteryl esters in apoB lipoproteins in LDLr-/- mice and a 3-fold increase in the apoE-/- mice compared with their counterparts with active LCAT. We conclude that LCAT deficiency in LDLr-/- and apoE-/- mice fed an atherogenic diet resulted in increased aortic cholesterol deposition, likely due to a reduction in plasma HDL, an increased saturation of cholesteryl esters in apoB lipoproteins and, in the apoE-/- background, an increased plasma concentration of apoB lipoproteins.
Furbee
James W
JW
Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Blvd., Winston-Salem, North Carolina 27157-1040, USA.
Sawyer
Janet K
JK
Parks
John S
JS
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001161:Arteriosclerosis / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D004036:Diet, Atherogenic; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000097:blood; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D010743:Phospholipids; D011973:Receptors, LDL; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase