Single-Cell RNA-Seq Reveals a Crosstalk between Hyaluronan Receptor LYVE-1-Expressing Macrophages and Vascular Smooth Muscle Cells.
Fabienne BurgerDaniela BaptistaAline RothKarim J BrandtRafaela Fernandes da SilvaFabrizio MontecuccoFrançois MachKapka MitevaPublished in: Cells (2022)
Background : Atherosclerosis is a chronic inflammatory disease where macrophages participate 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.
Keyphrases
- single cell
- rna seq
- gene expression
- liver fibrosis
- liver injury
- vascular smooth muscle cells
- coronary artery disease
- high throughput
- physical activity
- dna methylation
- endothelial cells
- aortic valve
- chronic kidney disease
- high fat diet
- oxidative stress
- wild type
- newly diagnosed
- bone marrow
- peripheral blood
- pulmonary artery
- skeletal muscle
- ejection fraction
- coronary artery
- genome wide
- microbial community
- patient safety
- high fat diet induced
- prognostic factors
- low density lipoprotein
- binding protein
- single molecule
- pulmonary arterial hypertension