Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen
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The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.
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LYVE-1+ macrophages can regulate vascular tone through interaction with mural cells.
“Prior studies have shown that LYVE-1 + macrophages can regulate vascular tone through interaction with mural cells [47].”
From Quantitative profiling of lifespan-dependent cell-cell communication potential reveals dynamic ligand-receptor network shifts across mouse tissues (2026) · cites this paper as [47]
Differentially expressed genes between macrophage states included Lyve1, Spp1, Slc40a1, and Spic.
“Differentially expressed genes between states included the hyaluronan receptor Lyve1 (Jordão et al., 2019a; Lim et al., 2018); Spp1, a potential regulator of phagocytosis in the brain (Hammond et al., 2019); Slc40a1, an iron transporter; and Spic, which marks red pulp macrophages (Haldar et al., 2014) and bone marrow macrophages (Kohyama et al., 2009) that we confirmed by IHC (Figure 5C, S5C).”
From A cellular and spatial map of the choroid plexus across brain ventricles and ages (2021) · cites this paper as Lim et al., 2018
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- Authors
- Lim, H. Y., Lim, S. Y., Tan, C. K., Thiam, C. H., Goh, C. C., Carbajo, D., Chew, S. H. S., See, P., Chakarov, S., Wang, X. N., Lim, L. H., Johnson, L. A., Lum, J., Fong, C. Y., Bongso, A., Biswas, A., Goh, C., Evrard, M., Yeo, K. P., Basu, R., Wang, J. K., Tan, Y., Jain, R., Tikoo, S., Choong, C., Weninger, W., Poidinger, M., Stanley, R. E., Collin, M., Tan, N. S., Ng, L. G., Jackson, D. G., Ginhoux, F., & Angeli, V.
- Affiliations
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- Agency for Science, Technology and Research (SG)
- Newcastle University (GB)
- John Radcliffe Hospital (GB)
- Albert Einstein College of Medicine (US)
- Centenary Institute (AU)
- Corresponding author
- Angeli, Véronique
- ORCID
- Lim, Hwee Ying
- Lim, Sheau Yng
- Goh, Chi Ching
- Carbajo, Daniel
- See, Peter
- Chakarov, Svetoslav
- Johnson, Louise A.
- Lum, Josephine
- Fong, Chui Yee
- Bongso, Ariff
- Biswas, Arijit
- Evrard, Maximilien
- Yeo, Kim Pin
- Wang, Jun Kit
- Tan, Yingrou
- Tikoo, Shweta
- Choong, Cleo
- Weninger, Wolfgang
- Poidinger, Michael
- Collin, Matthew
- Tan, Nguan Soon
- Ng, Lai Guan
- Jackson, David G.
- Ginhoux, Florent
- Angeli, Véronique
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 49
- Issue
- 2
- Pages
- 326-341.e7
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2883126472
- Cited by
- 384
- References
- 50
- Citations by year
- 2026: 40 · 2025: 50 · 2024: 54 · 2023: 61 · 2022: 73 · 2021: 47 · 2020: 36 · 2019: 19 · 2018: 4
- FWCI
- 14.65
- Type
- journal article
- Language
- en
- Update notices
- erratum (2018-12-18)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by-nc-nd)
- Funders
- EMBO (NRFI2017-02)
- National Medical Research Council (CBRGnov094)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- LYVE-1, hyaluronan receptor, arterial tone, arterial stiffness, smooth muscle cells, collagen deposition, MMP-9, CSF1R, aorta, leukocyte function
- MeSH terms
- Animals, Aorta, Collagen, Female, Glycoproteins, Humans, Hyaluronic Acid, Macrophages, Male, Mice, Inbred C57BL, Muscle, Smooth, Vascular, Receptors, Granulocyte-Macrophage Colony-Stimulating Factor, Mice, Knockout, Hyaluronan Receptors, Matrix Metalloproteinase 9, Membrane Transport Proteins, Myocytes, Smooth Muscle, Mice, Vascular Stiffness
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