title: Regulated Hyaluronan Synthesis by Vascular Cells.
abstract: Cellular microenvironment plays a critical role in several pathologies including atherosclerosis. Hyaluronan (HA) content often reflects the progression of this disease in promoting vessel thickening and cell migration. HA synthesis is regulated by several factors, including the phosphorylation of HA synthase 2 (HAS2) and other covalent modifications including ubiquitination and O-GlcNAcylation. Substrate availability is important in HA synthesis control. Specific drugs reducing the UDP precursors are able to reduce HA synthesis whereas the hexosamine biosynthetic pathway (HBP) increases the concentration of HA precursor UDP-N-acetylglucosamine (UDP-GlcNAc) leading to an increase of HA synthesis. The flux through the HBP in the regulation of HA biosynthesis in human aortic vascular smooth muscle cells (VSMCs) was reported as a critical aspect. In fact, inhibiting O-GlcNAcylation reduced HA production whereas increased O-GlcNAcylation augmented HA secretion. Additionally, O-GlcNAcylation regulates HAS2 gene expression resulting in accumulation of its mRNA after induction of O-GlcNAcylation with glucosamine treatments. The oxidized LDLs, the most common molecules related to atherosclerosis outcome and progression, are also able to induce a strong HA synthesis when they are in contact with vascular cells. In this review, we present recent described mechanisms involved in HA synthesis regulation and their role in atherosclerosis outcome and development.
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Viola
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Karousou
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: D'Angelo
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Caon
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: De Luca
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Passi
authors.affiliation: Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Vigetti