Novel mechanism of fluoride induced cardiovascular system injury by regulating p53/miR200c-3p during endothelial...

The impairment of the cardiovascular system by fluoride has attracted public health concern, and its toxic effects on ECs have garnered extensive research attention. However, epidemiological clues of fluoride induced cardiovascular injury are limited. The function of ECs is crucial for the early diagnosis of CVD, yet mechanisms through which fluoride disrupts endothelial function are still unclear.

To investigate the relationship between fluoride exposure and hypertension in population by epidemiological investigation. To explore the potential mechanism of functional injury of ECs induced by fluoride.

Epidemiological studies have shown that the risk of hypertension in study population increased with the increased of urinary fluoride concentration [OR = 1.565, 95%CI (1.143, 2.142)]. In rat model with fluorosis alongside a model of fluoride induced ECs injury, NaF led to anti-adhesion of ECs and barrier dysfunction. Notably, the expression levels of eNOS and NO were found to be decreased, while the expression levels of ACE, vWF, ICAM-1, VCAM-1 and ET-1 were elevated. Our findings also indicated that NaF induced oxidative stress in ECs, evidenced by significant increased in ROS and MDA levels and decreased protein expression of GPx4 and SOD activity. It was further found that NaF activated the p53/miR-200c-3p signaling axis via ROS, leading to endothelial dysfunction.

This study found that fluoride exposure was a risk factor for hypertension. In addition, fluoride could cause ECs dysfunction by inducing oxidative stress and activating p53/miR-200c-3p. These findings were helpful to further understand the mechanism of fluoride induced cardiovascular system injury and provide a theoretical basis for fluoride induced cardiovascular system injury.