| Title: |
Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells |
| Authors: |
Burger F.; Baptista D.; Roth A.; Brandt K. J.; da Silva R. F.; Montecucco F.; Mach F.; Miteva K. |
| Contributors: |
Burger, F.; Baptista, D.; Roth, A.; Brandt, K. J.; da Silva, R. F.; Montecucco, F.; Mach, F.; Miteva, K. |
| Publisher Information: |
MDPI |
| Publication Year: |
2022 |
| Collection: |
Università degli Studi di Genova: CINECA IRIS |
| Subject Terms: |
CCL24; LYVE-1; Osteogenic-like cell; Resident-like macrophage; Vascular calcification; VSMC transdifferentiation |
| Description: |
Background: Atherosclerosis is a chronic inflammatory disease where macrophages partici-pate in the progression of the disease. However, the role of resident-like macrophages (res-like) in the atherosclerotic aorta is not completely understood. Methods: A single-cell RNA sequencing analysis of CD45+ leukocytes in the atherosclerotic aorta of apolipoprotein E–deficient (Apoe−/−) mice on a normal cholesterol diet (NCD) or a high cholesterol diet (HCD), respecting the side-to-specific predisposition to atherosclerosis, was performed. A population of res-like macrophages expressing hyaluronan receptor LYVE-1 was investigated via flow cytometry, co-culture experiments, and immunofluorescence in human atherosclerotic plaques from carotid artery disease patients (CAD). Results: We identified 12 principal leukocyte clusters with distinct atherosclerosis disease-relevant gene expression signatures. LYVE-1+ res-like macrophages, expressing a high level of CC motif chemokine ligand 24 (CCL24, eotaxin-2), expanded under hypercholesteremia in Apoe−/− mice and promoted VSMC phenotypic modulation to osteoblast/chondrocyte-like cells, ex vivo, in a CCL24-dependent manner. Moreover, the abundance of LYVE-1+CCL24+ macrophages and elevated systemic levels of CCL24 were associated with vascular calcification and CAD events. Conclusions: LYVE-1 res-like macrophages, via the secretion of CCL24, promote the transdifferentiation of VSMC to osteogenic-like cells with a possible role in vascular calcification and likely a detrimental role in atherosclerotic plaque destabilization. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/35159221; info:eu-repo/semantics/altIdentifier/wos/WOS:000756121300001; volume:11:411; firstpage:1; lastpage:22; numberofpages:22; journal:CELLS; https://hdl.handle.net/11567/1069858 |
| DOI: |
10.3390/cells11030411 |
| Availability: |
https://hdl.handle.net/11567/1069858; https://doi.org/10.3390/cells11030411 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.7B9FEF64 |
| Database: |
BASE |