Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Atherosclerosis is a major lifestyle-related disease in advanced countries. In the lesion, intimal thickening causes narrowing of the vessel wall and forms a local hypoxic environment that exacerbates the progression of the disease. Proteoglycans (PGs) are macromolecules that consist of glycosaminoglycan chains attached to a core protein. PGs play an important role in the regulation of vascular functions. We have found that the core protein expression of biglycan, perlecan, and syndecan-1, the major PGs synthesized by bovine aortic endothelial cells, are reduced under hypoxic culture condition, but the extrapolation to human cells remains unclear. In this study, we used a human vascular endothelial cell line EA.hy926 cells and analyzed the expression of PGs under hypoxic conditions. In hypoxic condition, biglycan mRNA increased after 24 h, perlecan mRNA decreased in a time-dependent manner, and syndecan-1 mRNA showed no significant change. On the other hand, biglycan, perlecan, and syndecan-1 core protein expression were all reduced under hypoxic condition. These results suggest that the decrease in PGs core protein expression under hypoxic conditions is a common phenomenon independent of species. PGs bind to antithrombin III and various growth factors/cytokines, each of which has an important role in vascular antithrombogenicity and repair from injury by transmitting signals to cells via core proteins and glycosaminoglycans. Therefore, the decrease in PGs caused by hypoxia contribute to the development of vascular disorders in atherosclerosis.
