Atheroprotective flow and endothelial hyaluronan biosynthesis

The inner blood vessel surface is lined with an endothelial surface layer of at least 0.5 μm, 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 pulsatile blood flow, found at normal vessel sites increases the size of this surface layer in vivo, while it is significantly reduced at atheroprone regions with bidirectional low flow. This study was undertaken to reveal if endothelial hyaluronan synthesis via hyaluronan synthase 2 (HAS2) can be changed by different shear stress conditions in vitro, especially in regard to an atheroprotective flow profile. Human umbilical vein endothelial cells, exposed to constant, pulsatile, and bidirectional laminar flow in a cone‐and‐plate system, were analysed for HAS2 expression by real‐time RT‐PCR and immunoblotting, and for hyaluronan by ELISA. HAS2 mRNA and protein were found to be shear stress‐dependently increased via the PI3K‐Akt‐pathway in a transient manner. Especially atheroprotective flow induced enzyme and hyaluronan effectively, while low and bidirectional flow did not induce any differences as compared to static control cultures. These experiments provide a link between the production of a constitutive component of the endothelial surface layer by endothelial cells and different blood flow conditions.