Pancreatic carboxyl ester lipase: A circulating enzyme that modifies normal and oxidized lipoproteins in vitro

Raanan Shamir, William J. Johnson, Kelly Morlock-Fitzpatrick, Reza Zolfaghari, Ling Li, Eric Mas, Dominique Lombardo, Diane W. Morel, Edward A. Fisher

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Pancreatic carboxyl ester lipase (CEL) hydrolyzes cholesteryl esters (CE), triglycerides (TG), and lysophospholipids, with CE and TG hydrolysis stimulated by cholate. Originally thought to be confined to the gastrointestinal system, CEL has been reported in the plasma of humans and other mammals, implying its potential in vivo to modify lipids associated with LDL, HDL (CE, TG), and oxidized LDL (lysophosphatidylcholine, lysoPC). We measured the concentration of CEL in human plasma as 1.2±0.5 ng/ml (in the range reported for lipoprotein lipase). Human LDL and HDL3 reconstituted with radiolabeled lipids were incubated with purified porcine CEL without or with cholate (10 or 100 μM, concentrations achievable in systemic or portal plasma, respectively). Using a saturating concentration of lipoprotein- associated CE (4 μM), with increasing cholate concentration there was an increase in the hydrolysis of LDL- and HDL3-CE; at 100 μM cholate, the percent hydrolysis per hour was 32±2 and 1.6±0.1, respectively, indicating that CEL interaction varied with lipoprotein class. HDL3-TG hydrolysis was also observed, but was only ~ 510% of that for HDL3-CE at either 10 or 100 μM cholate. Oxidized LDL (OxLDL) is enriched with lysoPC, a proatherogenic compound. After a 4-h incubation with CEL, the lysoPC content of OxLDL was depleted 57%. Colocalization of CEL in the vicinity of OxLDL formation was supported by demonstrating in human aortic homogenate a cholate-stimulated cholesteryl ester hydrolytic activity inhibited by anti-human CEL IgG. We conclude that CEL has the capability to modify normal human LDL and HDL composition and structure and to reduce the atherogenicity of OxLDL by decreasing its lysoPC content.

Original languageEnglish (US)
Pages (from-to)1696-1704
Number of pages9
JournalJournal of Clinical Investigation
Volume97
Issue number7
DOIs
StatePublished - Apr 1 1996

Keywords

  • aorta
  • high density lipoprotein
  • low density lipoprotein
  • lysophosphatidyl choline
  • oxidized low density lipoprotein

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