title: Plasma carboxyl ester lipase activity modulates apolipoprotein B-containing lipoprotein metabolism in a transgenic mouse model.
abstract: Pancreatic carboxyl ester lipase (CEL) is in the plasma of many mammals, including humans and rats, but not mice. In vitro, CEL hydrolyzes cholesterol esters of apolipoprotein B-containing lipoproteins (apo B-Lp). To study the effect of CEL on metabolism of apo B-Lp and atherosclerosis in vivo, apo E-knockout (EKO) mice, which have high plasma levels of apo B-Lp and are prone to atherosclerosis, were made to secrete CEL into plasma by introducing a transgene containing a liver-specific promoter and rat CEL complementary DNA. Plasma CEL activity in EKO-CEL mice was comparable with that found in rats. Evidence of modification of apo B-Lp by plasma CEL in vivo was an increase in the free cholesterol to cholesterol ester ratio of apo B-Lp from mice on chow or a Western-type diet. In addition, plasma total cholesterol levels were elevated in EKO-CEL mice, with the elevation found exclusively in the apo B-Lp fraction. Associated with the increase in steady-state apo B-Lp levels was an increase in the plasma half-life of very low-density lipoproteins (VLDL) in EKO-CEL mice, measured by the clearance rate of injected VLDL. Interestingly, despite the increase of apo B-Lp, the atherosclerotic lesion did not differ between EKO and EKO-CEL mice on a Western-type diet. In summary, our results demonstrate that plasma CEL modulates apo B-Lp metabolism in vivo, resulting in reduced VLDL clearance and elevated plasma cholesterol levels.
authors.affiliation: Laboratory of Lipoprotein Research, Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. lili@uab.edu
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Weng
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood*; D050197:Atherosclerosis / Q000097:blood* / Q000201:enzymology*; D043182:Carboxylesterase / Q000097:blood* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000097:blood; D005260:Female; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D053419:Lipoproteins, IDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018709:Statistics, Nonparametric
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D002788:Cholesterol Esters; D008074:Lipoproteins; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D002784:Cholesterol; D043182:Carboxylesterase