title: Glycosaminoglycans and glucose prevent apoptosis in 4-methylumbelliferone-treated human aortic smooth muscle cells.
abstract: Smooth muscle cells (SMCs) have a pivotal role in cardiovascular diseases and are responsible for hyaluronan (HA) deposition in thickening vessel walls. HA regulates SMC proliferation, migration, and inflammation, which accelerates neointima formation. We used the HA synthesis inhibitor 4-methylumbelliferone (4-MU) to reduce HA production in human aortic SMCs and found a significant increase of apoptotic cells. Interestingly, the exogenous addition of HA together with 4-MU reduced apoptosis. A similar anti-apoptotic effect was observed also by adding other glycosaminoglycans and glucose to 4-MU-treated cells. Furthermore, the anti-apoptotic effect of HA was mediated by Toll-like receptor 4, CD44, and PI3K but not by ERK1/2.
authors.affiliation: Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell'Insubria, via JH Dunant 5, 21100 Varese, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vigetti
authors.forename: Manuela
authors.initials: M
authors.lastname: Rizzi
authors.forename: Paola
authors.initials: P
authors.lastname: Moretto
authors.forename: Sara
authors.initials: S
authors.lastname: Deleonibus
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Dreyfuss
authors.forename: Evgenia
authors.initials: E
authors.lastname: Karousou
authors.forename: Manuela
authors.initials: M
authors.lastname: Viola
authors.forename: Moira
authors.initials: M
authors.lastname: Clerici
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Hascall
authors.forename: Marco F
authors.initials: MF
authors.lastname: Ramoni
authors.forename: Giancarlo
authors.initials: G
authors.lastname: De Luca
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
mesh_terms: D001011:Aorta / Q000473:pathology*; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D005947:Glucose / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D006820:Hyaluronic Acid / Q000494:pharmacology*; D006923:Hymecromone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D051197:Toll-Like Receptor 4; D006923:Hymecromone; D006820:Hyaluronic Acid; D019869:Phosphatidylinositol 3-Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose