Abstract
BackgroundDiabetes 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.MethodsHUVECs 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.ResultsTransendothelial 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.ConclusionHigh-glucose stimulation upregulated MLC phosphorylation and increased endothelial permeability by activating the RhoA-ROCK signaling pathway in HUVECs in vitro.
Highlights
Diabetes mellitus is one of the most important risk factors for atherosclerosis
We examined the effects of blocking the RhoA-Rho-associated protein kinase (ROCK) signaling pathway using dominant negative RhoA and the specific ROCK inhibitor Y27632 on the high-glucose-induced increase in endothelial permeability
The administration of dominant negative RhoA (dnRhoA) or the ROCK inhibitor Y27632 significantly attenuated the effects of high-glucose medium (Table 1)
Summary
The mecha‐ nisms 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. Previous studies have demonstrated that high glucose can destroy endothelial function [1,2,3], which is an initiating condition for atherosclerosis. Rho family GTPases, especially RhoA, play an important role in maintaining and adjusting endothelial barrier function [4, 5]. Activation of RhoA enhances the activity of its downstream Rho kinase [Rho-associated protein kinase (ROCK)], which in turn induces myosin light chain (MLC) phosphorylation [6].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
