In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. suppl_1 ( 2016-05)
Abstract:
Procollagen C-endopeptidase enhancer protein 2 (PCPE2) modulates selective HDL cholesterol ester uptake by SR-BI. Ldlr-/-,Pcpe2-/- mice develop greater aortic atherosclerosis despite increased concentrations of enlarged plasma HDL, suggesting PCPE2 confers functionality to HDL for reverse cholesterol transport. PCPE2 is a 52 kDa glycoprotein encoded by PCOLCE2 gene most highly expressed in adipose tissue, heart and aorta. PCPE2 has 2 CUB domains separated by a short linker, with each CUB domain containing a beta-sandwich fold, mediating a variety of protein-protein interactions. PCPE2 also contains a C-terminal netrin-like domain that binds tightly to cell surface glycosaminoglycans accounting for its location in the extracellular matrix. Because of the strong inverse correlation between HDL and triglyceride levels, and the potential role of SR-BI in triglyceride-rich lipoprotein uptake we examined Ldlr-/-,Pcpe2-/-mice fed a Western diet for 25 weeks. Ldlr-/-,Pcpe2-/- mice showed 1.7 fold increase in plasma triglyceride concentrations when compared to age and gender matched Ldlr-/- mice. We also noted that despite similar body weights, Ldlr-/-,Pcpe2-/- visceral fat pad weight was reduced 60% (p 〈 0.001, n=9 per genotype) compared to Ldlr-/- mice, while subcutaneous fat pad weight was not significantly different. This maldistribution of adipose in Ldlr-/-,Pcpe2-/- was associated with increased fasting plasma glucose levels, elevated 25% (p 〈 0.02) over Ldlr-/- mice. In humans, analyses showed significant correlations of subcutaneous fat PCPE2 RNA expression with DEXA traits from the TwinsUK cohort; % android fat (p 〈 0.0002), % trunk fat (p 〈 0.0001) and % gynoid fat (p 〈 0.04). Additional correlations between PCPE2 mRNA abundance and candidate marker expression will also be presented using 53 human visceral fat samples. Overall these data suggest that PCPE2 plays an important role in regional fat deposition linking SR-BI mediated cholesterol ester uptake to adipose cell biology.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.36.suppl_1.50
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1494427-3
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