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Elsevier, Journal of Biological Chemistry, 40(286), p. 34497-34503, 2011

DOI: 10.1074/jbc.m111.266312

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Glycosaminoglycans and Glucose Prevent Apoptosis in 4-Methylumbelliferone-treated Human Aortic Smooth Muscle Cells*

Journal article published in 2011 by Davide Vigetti, Manuela Rizzi, Paola Moretto, Sara Deleonibus, Dreyfuss Jm, Jonathan M. Dreyfuss ORCID, Evgenia Karousou, Manuela Viola, Moira Clerici, Hascall Vc, Vincent C. Hascall, Ramoni Mf, Giancarlo De Luca, Marco F. Ramoni, Alberto Passi ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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.