Macrophage sortilin promotes LDL uptake, foam cell formation, and atherosclerosis.

ABSTRACT:

Rationale

Noncoding gene variants at the SORT1 locus are strongly associated with low-density lipoprotein cholesterol (LDL-C) levels, as well as with coronary artery disease. SORT1 encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apolipoprotein B-containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown.

Objective

To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis.

Methods and results

We crossed Sort1(-/-) mice onto a humanized Apobec1(-/-); hAPOB transgenic background and determined that Sort1 deficiency on this background had

SUBMITTER: Patel KM 

PROVIDER: S-EPMC4602371 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature