GPR182 promotes atherosclerosis via facilitating arterial lipid deposition
- 1University of Colorado Anschutz Medical Campus
Abstract
Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis; however, the molecular mechanisms underlying lipid plaque formation within the artery wall remain poorly understood. Here, we identify GPR182, a recently characterized lipoprotein receptor of the atypical chemokine receptor family, as a key mediator of lipid deposition in the aortic endothelium during atherosclerosis. Genetic depletion of GPR182 protects against atherosclerosis across multiple mouse models without altering circulating cholesterol levels or immune cell recruitment to plaques. GPR182 is expressed by aortic endothelial cells (ECs) and is further upregulated during disease progression. GPR182 mediates LDL uptake by aortic ECs both in vitro and in vivo. Blockade of GPR182 with a monoclonal antibody reduces lipid uptake in the aorta and attenuates disease progression under hypercholesterolemic conditions. Collectively, these findings identify endothelial GPR182 as a critical regulator of aortic lipid deposition and atherosclerotic plaque formation and support GPR182 inhibition as a promising therapy for atherosclerotic cardiovascular disease.
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BibTeX
@misc{terai2026gpr182,
title = {{GPR182 promotes atherosclerosis via facilitating arterial lipid deposition}},
author = {T. Terai and S. Doi and Z. Sun and Y. Sun and D. Fykstra and Y. Guo and Y. Hirasawa and J. Hu and M. Sho and R. Schulick and Y. Zhu},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.748866},
url = {https://www.biorxiv.org/content/10.64898/2026.09.15.748866v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - GPR182 promotes atherosclerosis via facilitating arterial lipid deposition
AU - T. Terai
AU - S. Doi
AU - Z. Sun
AU - Y. Sun
AU - D. Fykstra
AU - Y. Guo
AU - Y. Hirasawa
AU - J. Hu
AU - M. Sho
AU - R. Schulick
AU - Y. Zhu
PY - 2026
DA - 2026/09/15
PB - bioRxiv
DO - 10.64898/2026.09.15.748866
UR - https://www.biorxiv.org/content/10.64898/2026.09.15.748866v1
AB - Elevated circulating low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for atherosclerosis; however, the molecular mechanisms underlying lipid plaque formation within the artery wall remain poorly understood. Here, we identify GPR182, a recently characterized lipoprotein receptor of the atypical chemokine receptor family, as a key mediator of lipid deposition in the aortic endothelium during atherosclerosis. Genetic depletion of GPR182 protects against atherosclerosis across multiple mouse models without altering circulating cholesterol levels or immune cell recruitment to plaques. GPR182 is expressed by aortic endothelial cells (ECs) and is further upregulated during disease progression. GPR182 mediates LDL uptake by aortic ECs both in vitro and in vivo. Blockade of GPR182 with a monoclonal antibody reduces lipid uptake in the aorta and attenuates disease progression under hypercholesterolemic conditions. Collectively, these findings identify endothelial GPR182 as a critical regulator of aortic lipid deposition and atherosclerotic plaque formation and support GPR182 inhibition as a promising therapy for atherosclerotic cardiovascular disease.
ER -