The endothelium is covered with a relatively thick (0.5 to 1 mm) surface layer (ESL) which contains hyaluronic acid. In arteries, there is a correlation between disturbed blood flow (reduced wall shear stress), reduction of the ESL, and a predilection for arteriosclerosis. Therefore, this study was done to investigate if endothelial hyaluronan synthases (HAS) are regulated by shear stress and if hyaluronic acid has a role to prevent nanoplaque formation.

Human umbilical vein endothelial cells (HUVEC) were freshly isolated, grown to confluence, exposed to shear stress in a cone-and-plate device, and analysed for HAS by standard methods. Nanoplaque formation was measured by in situ ellipsometry.

Isoenzyme HAS2, highly expressed in endothelial cells, is further increased by shear stress on the mRNA- and protein level thus facilitating the production of hyaluronic acid. VLDL, IDL, and LDL form ternary complexes (nanoplaques) on proteoheparan sulfate-coated surfaces. Hyaluronic acid proved to be similarly effective in inhibiting this ternary complex formation as HDL.

These data support the hypothesis that the synthesis of hyaluronic acid by endothelial cells contributes to shear stress-dependent athero-protective mechanisms especially during the initiation of arteriosclerosis by blocking ternary complex formation.