Glycosaminoglycans and Glucose Prevent Apoptosis in 4-Methylumbelliferone-treated Human Aortic Smooth Muscle Cells |
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| Authors: | Davide Vigetti Manuela Rizzi Paola Moretto Sara Deleonibus Jonathan M Dreyfuss Evgenia Karousou Manuela Viola Moira Clerici Vincent C Hascall Marco F Ramoni Giancarlo De Luca Alberto Passi |
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| Institution: | From the ‡Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Università degli Studi dell''Insubria, via J. H. Dunant 5, 21100 Varese, Italy.;the §Harvard-Partners Center for Genetics and Genomics, Harvard Medical School, Boston, Massachusetts 02115, amd ;the ¶Biomedical Engineering ND20, The Cleveland Clinic, Cleveland, Ohio 44195 |
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| 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. |
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| Keywords: | Glycobiology Glycoprotein Glycosaminoglycan Hyaluronate Proteoglycan |
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