Role of vasodilator-stimulated phosphoprotein in human cytomegalovirus-induced hyperpermeability of human endothelial cells

Atherosclerosis (AS) is a common chronic vascular disease and epidemiological evidence demonstrates that infection is closely associated with the occurrence of AS, including infection by human cytomegalovirus (HCMV) and Chlamydophila pneumoniae. The aim of the present study was to investigate the effect of HCMV AD169 infection on the barrier function of human umbilical vein endothelial cells (HUVECs) and to understand the role of vasodilator-stimulated phosphoprotein (VASP) during this process. In cultured HUVEC-CRL-1730 cells, knockdown of VASP expression with small interfering (si)RNA-VASP resulted in impaired cellular barrier function. Furthermore, knockdown of Ras-related C3 botulinum toxin substrate 1 (Rac1) using siRNA-Rac1 could induce downregulation of VASP expression in HUVEC-CRL-1730 cells. Additionally, following the infection of the cells by HCMV, cellular morphological alterations could be observed under an inverted microscope, the mRNA and protein levels of Rac1 and VASP were transiently reduced, and what appeared to be a time-dependent impairment of the barrier function was observed. Finally, transfection of siRNA-VASP or siRNA-Rac1 into HCMV-infected HUVEC-CRL-1730 cells resulted in increased impairment of the cellular barrier function. Taken together, these data demonstrated that HCMV infection could induce impairment of the barrier function in monolayer HUVEC-CRL-1730 cells via interference with Rac1/VASP expression.