Host: The Japanese Society of Toxicology
Name : The 50th Annual Meeting of the Japanese Society of Toxicology
Date : June 19, 2023 - June 21, 2023
Cadmium is a toxic heavy metal widely present in the environment, and we are exposed to cadmium through diet and smoking unintentionally. Epidemiologically, cadmium is known as a risk factor for atherosclerosis and causes dysfunction of the endothelial cells covering the lumen of blood vessels. At the surface of endothelial cells, hyaluronan (HA) which is composed of N-acetylglucosamine and glucuronic acids, is synthesized as large HA of 1000-2000 kDa and small HA of about 100 kDa by three types of HA synthases (HAS1-3) and regulates cell growth and inflammatory responses. Since HA accumulates in atherosclerotic lesions, it is considered that HA contribute to the development and progression of cadmium-induced atherosclerosis. However, the effect of cadmium on HA synthesis in vascular endothelial cells remains unclear. In this study, we found that cadmium enhances HA synthesis and specifically upregulates HAS3 expression via activation of JNK-c-Jun pathway in vascular endothelial cells.
HAS3 is induced in early stage in atherosclerosis, and small HA promotes angiogenesis and inflammatory responses. Macrophages and T-lymphocytes accumulate in atherosclerotic lesions, and enhanced HA synthesis in vascular endothelial cells leads to recruitment of macrophages and T lymphocytes to the site of inflammation in a HA receptor CD44-dependent manner. Therefore, cadmium mediated HAS3 induction in vascular endothelial cells would contribute to the development and progression of atherosclerotic lesions by enhancing inflammation.
