A study to investigate radiation-induced and non-radiation-induced carotid atherosclerosis and endothelial dysfunction

Abstract

Both radiation and cardiovascular risk factors (CVRF) can lead to carotid atherosclerosis. The unstable carotid plaques are highly associated with cerebrovascular events. Therefore, detection and evaluation of carotid atherosclerosis and plaques characteristics are essential for individuals. Endothelial dysfunction is the primary injury for both radiation-/hyperglycaemia-induced carotid atherosclerosis. However, the underlying mechanism is unclear. This project aimed to investigate the feasibility of using a computer-assisted method to evaluate and differentiate the carotid plaque characteristics in radiation-/non-radiation-induced carotid atherosclerosis, and investigated the effects of radiation and high glucose on endothelial dysfunction and the possible signalling pathways involved. In human study, 107 post-RT nasopharyngeal carcinoma (NPC) patients and 110 CVRF subjects were recruited. The carotid intima-media thickness (CIMT) and carotid plaque characteristics (plaque formation, detailed plaque texture analysis) were assessed. The correlation of risk factors and carotid plaque characteristics was evaluated by multivariate model. Study results showed post-RT NPC patients had significantly higher CIMT (p=0.001), plaque formations (p<0.001) and locations (p<0.001) than CVRF subjects. Besides, radiation-induced carotid plaques had significantly more calcification (p=0.012), but lesser lipids (p=0.034) than non-radiation-induced carotid plaques. Moreover, age, radiation and number of CVRF were significantly associated with carotid atherosclerosis burden (p<0.001). Age was significantly associated with the amount of lipid and calcification within carotid plaques (p<0.001). In conclusion, post-RT NPC patients were more susceptible to carotid plaque formation, whereas CVRF subjects had carotid plaques with more lipids. In cell line study, the cell viability, tube formation ability and various protein expressing levels of HUVECs were detected at high/low glucose level, with/without 8Gy radiation. The results found that radiation suppressed cell viability (p<0.001), and the combined effects of radiation and high glucose increased angiogenesis. In conclusion, caspase-promoted apoptosis and increased angiogenesis are the main cellular responses in radiation-induced endothelial dysfunction.