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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aorta / pathology*
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Apoptosis*
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Cell Movement
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Cell Proliferation
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Glucose / metabolism*
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Glycoproteins / metabolism
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Glycosaminoglycans / metabolism*
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Humans
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Hyaluronan Receptors / biosynthesis
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Hyaluronic Acid / pharmacology*
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Hymecromone / analogs & derivatives*
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Hymecromone / pharmacology
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Inflammation
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Myocytes, Smooth Muscle / cytology*
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Oligonucleotide Array Sequence Analysis
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Phosphatidylinositol 3-Kinases / metabolism
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Toll-Like Receptor 4 / metabolism
Substances
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Glycoproteins
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Glycosaminoglycans
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Hyaluronan Receptors
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Toll-Like Receptor 4
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Hymecromone
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Hyaluronic Acid
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Phosphatidylinositol 3-Kinases
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Glucose