Summary
A bioRxiv preprint reports that the receptor GPR182 helps aortic endothelial cells take up LDL and promotes atherosclerotic plaque formation in multiple mouse models. Blocking the receptor with an antibody reduced aortic lipid uptake and disease progression under high-cholesterol conditions.
A bioRxiv preprint reports that the receptor GPR182 helps drive lipid accumulation in the artery wall during atherosclerosis. In experiments involving multiple mouse models, genetically depleting GPR182 reduced atherosclerosis without changing circulating cholesterol levels or the recruitment of immune cells into plaques.
The researchers also found that GPR182 is present in aortic endothelial cells—the cells lining the inside of blood vessels—and becomes more abundant as disease progresses. In laboratory and animal experiments, the receptor mediated uptake of low-density lipoprotein (LDL), the cholesterol-carrying particle commonly associated with atherosclerosis. Blocking GPR182 with a monoclonal antibody reduced lipid uptake in the aorta and slowed disease progression in mice under hypercholesterolemic conditions.
The work was posted as a preprint on September 21, 2026, so it has not yet undergone peer review.
A receptor involved in lipid deposition
Atherosclerosis develops when lipids and other material accumulate within artery walls, forming plaques that can restrict blood flow. Elevated circulating LDL cholesterol is an established risk factor, but the steps that determine how cholesterol moves from the bloodstream into the artery wall are more specific than a blood-cholesterol measurement alone.
The study focuses on GPR182, which the authors describe as a recently characterised lipoprotein receptor belonging to the atypical chemokine receptor family. Its activity in aortic endothelial cells provides a possible connection between circulating LDL and the initial deposition of lipid in the vessel wall.
The findings are notable because GPR182 depletion protected mice from disease while leaving circulating cholesterol levels unchanged. This pattern points to a role for the receptor in handling or transporting LDL at the artery surface, rather than simply altering the amount of cholesterol circulating in the blood. That interpretation is consistent with the researchers’ direct observations of GPR182-dependent LDL uptake in endothelial cells and aortas.
Genetic and antibody experiments
The researchers used genetic depletion of GPR182 in multiple mouse models of atherosclerosis. They assessed disease development alongside circulating cholesterol and immune-cell recruitment to plaques. The genetic intervention was associated with less atherosclerosis, while the abstract reports no change in those two systemic or inflammatory measurements.
The team then tested whether GPR182 could be blocked pharmacologically. A monoclonal antibody directed against the receptor reduced lipid uptake in the aorta and attenuated disease progression when the mice were exposed to hypercholesterolemic conditions. Together with the in-vitro experiments, these results support a model in which endothelial GPR182 contributes to arterial lipid deposition.
The authors describe GPR182 inhibition as a promising therapeutic approach for atherosclerotic cardiovascular disease. At this stage, however, the evidence is preclinical: it comes from cultured cells and mouse models, not from human participants or clinical trials. Whether the same mechanism operates in people, and whether blocking GPR182 would be effective and safe as a treatment, will require further research.
The authors disclose that three researchers have a patent filing related to the project and that Yuwen Zhu consults for DynamiCure Biotechnology. The study was funded in part by the US National Institutes of Health and the Melanoma Research Foundation.