Cadmium exposure induces inflammation, oxidative stress and DNA damage in HUVEC and promotes THP-1 adhesion: A possible mechanism on the formation of atherosclerotic plaque.

Observational studies have shown that cadmium exposure increases the risk of cardiovascular disease, but the underlying mechanism is still unclear. Atherosclerotic plaque can cause vascular obstruction, which is important for the death from cardiovascular disease. Cell damage and monocyte adhesion are two early events in atherosclerotic plaque formation that can be induced by cadmium exposure, but the mechanism remains to be determined. This study was carried out to investigate the toxicity of cadmium in HUVECs and the effect of cadmium on the adhesion of THP-1 cells, and further explored the possible mechanisms. Rhodamine staining, DCFH-DA staining, Hoechst33258 staining, morphological observation and western blot were used to detect mitochondrial membrane potential, ROS, apoptosis, cell adhesion, signaling pathways and cell adhesion factors respectively. The results indicated that cadmium exposure increased the level of ROS, activated MAPK signaling pathway and resulted in cellular oxidative stress in HUVECs. Exposure to cadmium made nuclear shrinkage, activated DNA damage response pathways and mitochondria-mediated intrinsic apoptosis pathway in HUVECs. Cadmium exposure activated the NLRP3 inflammasome and NF-κB signaling pathway, led to the upregulation of inflammatory cytokines in HUVECs. In addition, cadmium exposure also upregulated the adhesion factors including ICAM-1, VCAM-1 and E-Selectin via NF-κB signaling pathway and resulted in the adhesion of THP-1 cells. The present study elucidated that cadmium could damage the HUVECs and promote the adhesion of THP-1 cells, which clarified the toxicity of cadmium in HUVECs and revealed the possible mechanism for the occurrence of cardiovascular disease induced by cadmium.