title: Smooth muscle cells in human atherosclerotic plaques secrete and proliferate in response to high mobility group box 1 protein.
abstract: High mobility group box 1 protein (HMGB1) is a chromatin component leaked out by necrotic cells and actively secreted by activated myeloid cells. The extracellular protein is a potent mediator of tissue remodeling. We show here that human atherosclerotic plaques, but not normal arteries, produce extracellular HMGB1. Secreted HMGB1 originates from endothelial cells, by neointimal foam cells, and also smooth muscle cells (SMCs). SMCs are an unexpected source for secreted HMGB1, since they normally express much lower amounts of HMGB1 than other cells types, and they do not secrete it. However, cultured SMCs actively secrete HMGB1 after cholesterol loading. In turn, in response to HMGB1, SMCs proliferate, migrate, and secrete more HMGB1. Thus, SMCs are both a source and a target of HMGB1; blocking HMGB1 secretion by SMCs can be an important strategy for treatment of atherosclerotic disease and in particular restenosis.
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Porto
authors.forename: Roberta
authors.initials: R
authors.lastname: Palumbo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pieroni
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Aprigliano
authors.forename: Roberto
authors.initials: R
authors.lastname: Chiesa
authors.forename: Francesca
authors.initials: F
authors.lastname: Sanvito
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein