ApoC-III Glycoforms Are Differentially Cleared by Hepatic TRL (Triglyceride-Rich Lipoprotein) Receptors

Arteriosclerosis, Thrombosis, and Vascular Biology
Natalie C KegulianPhilip L S M Gordts

Abstract

ApoC-III (apolipoprotein C-III) glycosylation can predict cardiovascular disease risk. Higher abundance of disialylated (apoC-III2) over monosialylated (apoC-III1) glycoforms is associated with lower plasma triglyceride levels. Yet, it remains unclear whether apoC-III glycosylation impacts TRL (triglyceride-rich lipoprotein) clearance and whether apoC-III antisense therapy (volanesorsen) affects distribution of apoC-III glycoforms. Approach and Results: To measure the abundance of human apoC-III glycoforms in plasma over time, human TRLs were injected into wild-type mice and mice lacking hepatic TRL clearance receptors, namely HSPGs (heparan sulfate proteoglycans) or both LDLR (low-density lipoprotein receptor) and LRP1 (LDLR-related protein 1). ApoC-III was more rapidly cleared in the absence of HSPG (t1/2=25.4 minutes) than in wild-type animals (t1/2=55.1 minutes). In contrast, deficiency of LDLR and LRP1 (t1/2=56.1 minutes) did not affect clearance of apoC-III. After injection, a significant increase in the relative abundance of apoC-III2 was observed in HSPG-deficient mice, whereas the opposite was observed in mice lacking LDLR and LRP1. In patients, abundance of plasma apoC-III glycoforms was assessed after placebo or vola...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Endocrinology·Jan BorénMarja-Riitta Taskinen
Sep 5, 2020·Cardiovascular Research·Angela PirilloGiuseppe Danilo Norata
Jan 23, 2021·International Journal of Molecular Sciences·Ismael Valladolid-AcebesLisa Juntti-Berggren
Oct 25, 2021·Journal of Proteomics·Marina RodríguezJosep Ribalta

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