LUR1 (SPRING1) promotes sortilin-induced macrophage lipid accumulation and aortic atherosclerosis via furin maturation.

Authors

Yuncheng Lv, Xiaoming Fan, Chuangbiao Lin, Huijuan Li, Yun Wang, Xiaping Jiang, Xiangyang Tang, Fang Liu

Published in

Biochimica et biophysica acta. Molecular and cell biology of lipids. Pages 159778. Oct 18, 2026. Epub Oct 18, 2026.

Abstract

This study was undertaken to investigate the contributions of largely Golgi-localized proteins-lipid uptake regulator 1 (LUR1, SPRING1), the protease furin, and sortilin-in oxidized low-density lipoprotein (ox-LDL)-treated macrophages and atherosclerotic mouse models.
Bioinformatics analysis was employed to predict the interaction between LUR1 and furin and their potential involvement in AS. The binding of LUR1 to furin was detected using a co-immunoprecipitation (Co-IP) assay. Gene and protein expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot in THP-1 macrophages transfected with recombinant lentiviruses. Cellular lipid content was measured by colorimetry, and lipid droplets were evaluated by Oil Red O staining. Plasma lipid profiles were measured using an enzymatic oxidation method. Histological staining was performed to investigate aortic atherosclerotic lesions in male LDLR^-/- mice fed a high-fat diet (HFD).
LUR1 increased the expression and maturation of macrophage sortilin. Co-IP confirmed LUR1-furin binding. The mRNA and protein levels of furin and sortilin were increased upon LUR1 OE, while the ratios of pro-furin/mature-furin and pro-sortilin/total-sortilin decreased, thereby enhancing lipid uptake in macrophages. Infection with adeno-associated virus 9 (AAV9)-LUR1 elevated plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), and increased lipid deposition and AS plaque area in the vessel walls of male HFD-fed LDLR^-/- mice.
LUR1 was implicated in furin/sortilin maturation, accelerating macrophage lipid accumulation and the progression of aortic AS.

PMID:
42893749
Bibliographic data and abstract were imported from PubMed on 19 Oct 2026.

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