Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins

Kelli L Sylvers-Davie; Kaleb C Bierstedt; Michael J Schnieders; Brandon S J Davies

doi:10.1038/s41598-024-54705-6

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Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins

Journal article

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Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins

Kelli L Sylvers-Davie, Kaleb C Bierstedt, Michael J Schnieders and Brandon S J Davies

Scientific reports, Vol.14(1), 4246

02/20/2024

DOI: 10.1038/s41598-024-54705-6

PMCID: PMC10879187

PMID: 38379026

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Abstract

High levels of HDL-C are correlated with a decreased risk of cardiovascular disease. HDL-C levels are modulated in part by the secreted phospholipase, endothelial lipase (EL), which hydrolyzes the phospholipids of HDL and decreases circulating HDL-C concentrations. A 584C/T polymorphism in LIPG, the gene which encodes EL, was first identified in individuals with increased HDL levels. This polymorphism results in a T111I point mutation the EL protein. The association between this variant, HDL levels, and the risk of coronary artery disease (CAD) in humans has been extensively studied, but the findings have been inconsistent. In this study, we took a biochemical approach, investigating how the T111I variant affected EL activity, structure, and stability. Moreover, we tested whether the T111I variant altered the inhibition of phospholipase activity by angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4), two known EL inhibitors. We found that neither the stability nor enzymatic activity of EL was altered by the T111I variant. Moreover, we found no difference between wild-type and T111I EL in their ability to be inhibited by ANGPTL proteins. These data suggest that any effect this variant may have on HDL-C levels or cardiovascular disease are not mediated through alterations in these functions.

Angiopoietin-Like Protein 3

Angiopoietin-like Proteins - genetics

Angiopoietins

Cardiovascular Diseases

Cholesterol, HDL - metabolism

Humans

Lipase - genetics

Lipase - metabolism

Phospholipases

Details

Title: Subtitle: Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins
Creators: Kelli L Sylvers-Davie - University of Iowa
Kaleb C Bierstedt - University of Iowa
Michael J Schnieders - University of Iowa
Brandon S J Davies - Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa, IA, 52242, USA. Brandon-davies@uiowa.edu
Resource Type: Journal article
Publication Details: Scientific reports, Vol.14(1), 4246
DOI: 10.1038/s41598-024-54705-6
PMID: 38379026
PMCID: PMC10879187
NLM abbreviation: Sci Rep
eISSN: 2045-2322
Grant note: R01HL162698 / NIH HHS R01DC012049 / NIH HHS T32DK112751 / NIH HHS
Language: English
Date published: 02/20/2024
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Chemical and Biochemical Engineering
Record Identifier: 9984560418002771

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