Effects of high glucose on human umbilical vein endothelial cell permeability and myosin light chain phosphorylation.

BACKGROUND

Diabetes mellitus is one of the most important risk factors for atherosclerosis. However, the mechanisms underlying high-glucose-induced atherosclerosis remain unclear. This study was designed to observe the effects of high-glucose stimulation on the permeability of cultured human umbilical vein endothelial cells (HUVECs), and to explore the effects of RhoA-Rho-associated protein kinase (ROCK) signal transduction pathway activation and myosin light chain (MLC) phosphorylation.

METHODS

HUVECs were cultured in conventional M199 medium to produce endothelial cell monolayers, and stimulated with high-glucose-M199 medium. The transmembrane transport of dextran and THP-1 cells and levels of MLC phosphorylation were measured. The effects of blocking the RhoA-ROCK pathway using dnRhoA or the ROCK inhibitor Y27632 on dextran and THP-1 transport and MLC phosphorylation were observed.

RESULTS

Transendothelial migration of dextran and THP-1 cells were significantly increased by stimulation of HUVEC monolayers with high glucose (P < 0.05). This effect was attenuated by treatment with dnRhoA or Y27632.

CONCLUSION

High-glucose stimulation upregulated MLC phosphorylation and increased endothelial permeability by activating the RhoA-ROCK signaling pathway in HUVECs in vitro.