title: Nestin(+) cells direct inflammatory cell migration in atherosclerosis.
abstract: Atherosclerosis is a leading death cause. Endothelial and smooth muscle cells participate in atherogenesis, but it is unclear whether other mesenchymal cells contribute to this process. Bone marrow (BM) nestin(+) cells cooperate with endothelial cells in directing monocyte egress to bloodstream in response to infections. However, it remains unknown whether nestin(+) cells regulate inflammatory cells in chronic inflammatory diseases, such as atherosclerosis. Here, we show that nestin(+) cells direct inflammatory cell migration during chronic inflammation. In Apolipoprotein E (ApoE) knockout mice fed with high-fat diet, BM nestin(+) cells regulate the egress of inflammatory monocytes and neutrophils. In the aorta, nestin(+) stromal cells increase ∼30 times and contribute to the atheroma plaque. Mcp1 deletion in nestin(+) cells-but not in endothelial cells only- increases circulating inflammatory cells, but decreases their aortic infiltration, delaying atheroma plaque formation and aortic valve calcification. Therefore, nestin expression marks cells that regulate inflammatory cell migration during atherosclerosis.
authors: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.|Grupo de Fisiopatología Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), 41013 Seville, Spain.
authors: Raquel
authors: R
authors: Del Toro
authors: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
authors: Raphael
authors: R
authors: Chèvre
authors: Centro de Investigación Cardiovascular (CSIC-ICCC), IIB-Sant Pau, 08025 Barcelona, Spain.
authors: Cristina
authors: C
authors: Rodríguez
authors: Grupo de Fisiopatología Cardiovascular, Instituto de Biomedicina de Sevilla (IBIS), 41013 Seville, Spain.
authors: Antonio
authors: A
authors: Ordóñez
authors: Centro de Investigación Cardiovascular (CSIC-ICCC), IIB-Sant Pau, 08025 Barcelona, Spain.
authors: José
authors: J
authors: Martínez-González
authors: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.
authors: Vicente
authors: V
authors: Andrés
authors: Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain.|Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, and National Health Service Blood and Transplant, Cambridge Biomedical Campus, CB2 0PT Cambridge, UK.
authors: Simón
authors: S
authors: Méndez-Ferrer
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D018932:Chemokine CCL2 / Q000235:genetics*; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D008648:Mesoderm / Q000166:cytology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology; D064231:Nestin / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D058226:Plaque, Atherosclerotic / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C577485:Nes protein, mouse; D064231:Nestin