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December 8, 2016eLifeOpen Access

The angiopoietin-like protein ANGPTL4 catalyzes unfolding of the hydrolase domain in lipoprotein lipase and the endothelial membrane protein GPIHBP1 counteracts this unfolding

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Population

Molecular models/proteins (lipoprotein lipase [LPL], ANGPTL4, and endothelial membrane protein GPIHBP1)

Comparison

ANGPTL4 and its common polymorphic variant vs Absence of GPIHBP1 or wild-type ANGPTL4

Design

Preclinical

Authors

SMSimon MyslingKKKristian Kølby KristensenMLMikael Larsson

Discussion

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Overview

May inform ANGPTL4-targeted triglyceride therapies; leaves open human translation and cardiovascular outcomes.

Structured PICO

P
Population
Molecular models/proteins (lipoprotein lipase [LPL], ANGPTL4, and endothelial membrane protein GPIHBP1)
I
Intervention
ANGPTL4 and its common polymorphic variant (Glu-to-Lys substitution)
C
Comparator
Absence of GPIHBP1 or wild-type ANGPTL4
O
Outcome
Unfolding of the LPL hydrolase domain and LPL activitysurrogate

Elucidates the molecular basis for LPL regulation by ANGPTL4 and GPIHBP1, explaining the mechanism by which a clinically relevant ANGPTL4 variant lowers plasma triglycerides.

Cite This Study

Mysling et al. (2016) studied this question.

synapsesocial.com/papers/6a82c2987a209f4aae23bb40https://doi.org/10.7554/elife.20958
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Angiopoietin-like Protein 4 Inhibition of Lipoprotein Lipase2013 · 87 citations
  2. 2GPIHBP1 stabilizes lipoprotein lipase and prevents its inhibition by angiopoietin-like 3 and angiopoietin-like 42009 · 125 citations
  3. 3The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain2016 · 99 citations
  4. 4ANGPTL4 mediates shuttling of lipid fuel to brown adipose tissue during sustained cold exposure2015 · 134 citations
  5. 5GPIHBP1, a GPI-anchored protein required for the lipolytic processing of triglyceride-rich lipoproteins2008 · 57 citations