Control of very low-density lipoprotein secretion by N-ethylmaleimide-sensitive factor and miR-33.

ABSTRACT:

Rationale

Several reports suggest that antisense oligonucleotides against miR-33 might reduce cardiovascular risk in patients by accelerating the reverse cholesterol transport pathway. However, conflicting reports exist about the impact of anti-miR-33 therapy on the levels of very low-density lipoprotein-triglycerides (VLDL-TAG).

Objective

We test the hypothesis that miR-33 controls hepatic VLDL-TAG secretion.

Methods and results

Using therapeutic silencing of miR-33 and adenoviral overexpression of miR-33, we show that miR-33 limits hepatic secretion of VLDL-TAG by targeting N-ethylmaleimide-sensitive factor (NSF), both in vivo and in primary hepatocytes. We identify conserved sequences in the 3'UTR of NSF as miR-33 responsive elements and show that Nsf is specifical

SUBMITTER: Allen RM 

PROVIDER: S-EPMC4108429 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature