Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 286, Issue 40, Pages 34497-34503Publisher
ELSEVIER
DOI: 10.1074/jbc.M111.266312
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Funding
- Centro Grandi Attrezzature per la Ricerca Biomedica Universita degli Studi dell'Insubria
- PhD School in Biological and Medical Sciences
- University of Insubria (FAR)
- Centro Interuniversitario di Biotecnologie
- Fondazione Comunitaria del Varesotto-ONLUS
- Centro Insubre di Biotecnologie per la Salute Umana
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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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