Lipoprotein Receptor-Related Protein Function in Vascular Biology

Lipoprotein receptor-related proteins, chiefly LRP1, are multifunctional endocytic receptors widely expressed in the vasculature. They mediate the clearance of lipoprotein remnants, modulate signalling pathways and influence the homeostasis of endothelial and smooth muscle cells. In endothelial cells, LRP1 has emerged not only as a scavenger receptor but also as a co-activator of nuclear receptors, thus integrating lipid metabolism with gene transcription. In vascular smooth muscle cells, LRP1 restrains pathological remodelling by attenuating angiotensin II-mediated signalling, thereby preserving vessel integrity and preventing aneurysm formation. Beyond lipid handling, LRP1 orchestrates inflammatory responses in macrophages through an intracellular cascade that promotes cholesterol efflux and dampens cytokine production. These diverse roles underpin its central position in the development of atherosclerosis, aneurysms and vascular inflammation, highlighting the receptor’s potential as both a biomarker and a therapeutic target in cardiovascular disease.

Research from Nature Portfolio

Recent work has demonstrated that endothelial LRP1 coordinates systemic energy homeostasis by acting as a transcriptional co-activator of PPARγ. Endothelium-specific deletion of LRP1 in mice improves glucose tolerance and lipid profiles under high-fat diet challenge, coupled with increased oxygen consumption. Mechanistically, the intracellular domain of LRP1 translocates to the nucleus and enhances PPARγ-driven gene expression, revealing a direct role for a lipoprotein receptor in vascular gene regulation. This finding expands the paradigm of LRP1 beyond endocytosis to include dynamic control of vascular metabolism and underpins its relevance to cardiometabolic health.

Lipoprotein Receptor-Related Protein Function in Vascular Biology publication trend

The graph below shows the total number of articles in lipoprotein receptor-related protein function in vascular biology across all publications each year (not limited to Nature Index journals).

Technical terms

LRP1: A large endocytic receptor that binds lipoproteins and proteases, integrating clearance functions with intracellular signalling.

Endothelial cell: The monolayer of cells lining the interior surface of blood vessels, crucial for vascular homeostasis and barrier function.

Vascular smooth muscle cell (vSMC): Contractile cells in the vessel wall that regulate tone and undergo remodelling in vascular diseases.

Soluble LRP1 (sLRP1): A cleaved circulating form of LRP1 detectable in plasma, reflecting receptor activity and vascular inflammation.

Neointima: A newly formed inner vascular layer composed of proliferating smooth muscle cells, often associated with restenosis and vessel narrowing.

References

1. Soluble low-density lipoprotein receptor-related protein 1 as a surrogate marker of carotid plaque inflammation assessed by 18F-FDG PET in patients with a recent ischemic stroke. Journal of Translational Medicine (2023).
2. LRP1 protects against excessive superior mesenteric artery remodeling by modulating angiotensin II-mediated signaling. JCI Insight (2023).
3. LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis. eLife (2017).
4. Endothelial LRP1 regulates metabolic responses by acting as a co-activator of PPARγ. Nature Communications (2017).
5. The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation. International Journal of Molecular Sciences (2018).