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Hyaluronan Receptor LYVE-1-Expressing Macrophages Maintain Arterial Tone through Hyaluronan-Mediated Regulation of Smooth Muscle Cell Collagen

2018; Cell Press; Volume: 49; Issue: 2 Linguagem: Inglês

10.1016/j.immuni.2018.06.008

1097-4180

Hwee Ying Lim, Sheau Yng Lim, Chek Kun Tan, Chung Hwee Thiam, Chi Ching Goh, Daniel Carbajo, Samantha Chew, Peter See, Svetoslav Chakarov, Xiao Nong Wang, Li Hui Lim, Louise A. Johnson, Josephine Lum, Chui‐Yee Fong, Ariff Bongso, Arijit Biswas, Chern Goh, Maximilien Evrard, Kim Pin Yeo, Ranu Basu, Jun Kit Wang, Yingrou Tan, Rohit Jain, Shweta Tikoo, Cleo Choong, Wolfgang Weninger, Michael Poidinger, Richard Stanley, Matthew Collin, Nguan Soon Tan, Lai Guan Ng, David G. Jackson, Florent Ginhoux, Véronique Angeli,

Proteoglycans and glycosaminoglycans research

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.