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

作者:Vigetti Davide; Rizzi Manuela; Moretto Paola; Deleonibus Sara; Dreyfuss Jonathan M; Karousou Evgenia; Viola Manuela; Clerici Moira; Hascall Vincent C; Ramoni Marco F; De Luca Giancarlo; Passi Alberto*
来源:JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, 286(40): 34497-34503.
DOI:10.1074/jbc.M111.266312

摘要

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.

  • 出版日期2011-10-7