Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition

Article Article scientifique Article Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition eng 2023-10-31 author Cardoso Dos Santos Luis Miguel 0000-0003-2971-6515 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 869480 author Azar Pascal 0000-0002-0022-0367 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 970290 Département de pathologie et immunologie (PATIM) author Brun Cécile Geneva University Hospitals, University of Geneva, Geneva, Switzerland. 585985 author Konig Stéphane 0000-0002-0801-279X Department of Neuroscience, University of Geneva, Geneva, Switzerland. 133957 Structure enseignement (ENSI) author Baertschi Angela Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 23608 author Baertschi Alex Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland. 110207 Décanat et administration de la faculté de médecine (ADMED) author Chaabane Chiraz Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 668795 author Piallat Marie-Luce 0000-0001-8408-8932 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. Marie-Luce.Piallat@unige.ch. 23951 Département de pathologie et immunologie (PATIM) 18736 10.1038/s41598-023-45470-z 37907514 2045-2322 PMC10618247 https://www.nature.com/articles/s41598-023-45470-z During atherosclerotic plaque formation, smooth muscle cells (SMCs) switch from a contractile/differentiated to a synthetic/dedifferentiated phenotype. We previously isolated differentiated spindle-shaped (S) and dedifferentiated rhomboid (R) SMCs from porcine coronary artery. R-SMCs express S100A4, a calcium-binding protein. We investigated the role of apelin in this phenotypic conversion, as well as its relationship with S100A4. We found that apelin was highly expressed in R-SMCs compared with S-SMCs. We observed a nuclear expression of apelin in SMCs within experimentally-induced intimal thickening of the porcine coronary artery and rat aorta. Plasmids targeting apelin to the nucleus (N. Ap) and to the secretory vesicles (S. Ap) were transfected into S-SMCs where apelin was barely detectable. Both plasmids induced the SMC transition towards a R-phenotype. Overexpression of N. Ap, and to a lesser degree S. Ap, led to a nuclear localization of S100A4. Stimulation of S-SMCs with platelet-derived growth factor-BB, known to induce the transition toward the R-phenotype, yielded the direct interaction and nuclear expression of both apelin and S100A4. In conclusion, apelin induces a SMC phenotypic transition towards the synthetic phenotype. These results suggest that apelin acts via nuclear re-localization of S100A4, raising the possibility of a new pro-atherogenic relationship between apelin and S100A4. Animals Apelin / genetics Apelin / metabolism Atherosclerosis / metabolism Cell Movement Cells, Cultured Myocytes, Smooth Muscle / metabolism Phenotype Rats Swine Dewey 616.8 Dewey 612 Dewey 616.07 Swiss National Science Foundation S100A4 is a key player of smooth muscle cell phenotypic transition: implications for atherosclerosis 185370 CH Projects 137 Département de pathologie et immunologie 21F 134 Département de physiologie cellulaire et métabolisme 21C 53 Département de neurosciences fondamentales 21A false 380 Bochaton-Piallat Marie-Luce (pathologie et immunologie) 646 1232 Régénération du muscle squelettique 986 Scientific reports 13 1 1444d6ed-1808-4b8d-8722-24f2e732834c Article (Published version) Public Article_scientifique_from_crossref.pdf 4992950 application/pdf CC BY-4.0 86c887b1e70e4163b852123ebb9336351cb18ab1e668e8ae488facd770c48c63 00884a62-c6da-40cb-ab6e-5c8518f00363 Supplemental data Public 41598_2023_45470_MOESM1_ESM.pdf 2550535 application/pdf d00b300584a75cf431767a451589dcb30864cb2a28353935b10e8142e0965713 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Apelin is expressed in intimal smooth muscle cells and promotes their phenotypic transition	Scientific reports			2023	60	55

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