title: Shear stress increases endothelial hyaluronan synthase 2 and hyaluronan synthesis especially in regard to an atheroprotective flow profile.
abstract: Recent studies revealed that in vivo the inner blood vessel surface is lined with an endothelial surface layer at least 0.5 μm thick, which serves as an aegis, protecting the vessel wall from arteriosclerosis. Hyaluronan seems to be a constitutive component in regard to the atheroprotective properties of this surface structure. It has been shown that arterial pulsatile laminar blood flow increases the thickness of this surface layer in vivo, while it is significantly reduced at atheroprone regions with disturbed flow. This study was undertaken to reveal whether endothelial hyaluronan synthesis via hyaluronan synthase 2 (HAS2) can be changed by different shear stress conditions in vitro, especially in regard to an undisturbed, arterial-like pulsatile flow profile. Human umbilical vein endothelial cells, exposed to constant or pulsatile shear stress in a cone-and-plate system, were analysed for HAS2 expression by real-time RT-PCR and immunoblotting, and for hyaluronan by ELISA. Hyaluronan synthase 2 mRNA and protein were found to be transiently increased in a shear stress-dependent manner via the phosphatidylinositol 3-kinase-Akt pathway. Especially pulsatile, arterial-like shear stress conditions induced enzyme and hyaluronan effectively, while lower shear stress that continuously changed its direction did not induce any differences in comparison with control cultures not exposed to shear stress. These experiments provide a link between the production of a constitutive component of the endothelial surface layer by endothelial cells and blood flow.
authors.affiliation: Charité, Campus Benjamin Franklin, Institute of Physiology, Thielallee 71, 14195 Berlin, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Maroski
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Vorderwülbecke
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Fiedorowicz
authors.forename: Luis
authors.initials: L
authors.lastname: Da Silva-Azevedo
authors.forename: Günter
authors.initials: G
authors.lastname: Siegel
authors.forename: Alex
authors.initials: A
authors.lastname: Marki
authors.forename: Axel Radlach
authors.initials: AR
authors.lastname: Pries
authors.forename: Andreas
authors.initials: A
authors.lastname: Zakrzewicz
mesh_terms: D001161:Arteriosclerosis / Q000517:prevention & control*; D002867:Chromones / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000096:biosynthesis*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D009025:Morpholines / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011673:Pulsatile Flow; D013314:Stress, Mechanical
chemical_list: D002867:Chromones; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases