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Uric acid (UA) accumulation triggers endothelial dysfunction, oxidative stress, and inflammation. Histone deacetylase (HDAC) plays a vital role in regulating the pathological processes of various diseases. However, the influence of HDAC inhibitor on UAinduced vascular endothelial cell injury (VECI) remains undefined. Hence, this study aimed to investigate the effect of HDACs inhibition on UA-induced vascular endothelial cell dysfunction and its detailed mechanism. UA was used to induce human umbilical vein endothelial cell (HUVEC) injury. Meanwhile, potassium oxonate-induced and hypoxanthine-induced hyperuricemia mouse models were also constructed. A broad-spectrum HDAC inhibitor trichostatin A (TSA) or selective HDAC6 inhibitor TubastatinA (TubA) was given to HUVECs or mice to determine whether HDACs can affect UA-induced VECI. The results showed pretreatment of HUVECs with TSA or HDAC6 knockdown-attenuated UAinduced VECI and increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a. These effects could be reversed by FGF21 knockdown. In vivo, both TSA and TubA reduced inflammation and tissue injury while increased FGF21 expression and phosphorylation of AKT, eNOS, and FoxO3a in the aortic and renal tissues of hyperuricemia mice. Therefore, HDACs, especially HDAC6 inhibitor, alleviated UA-induced VECI through upregulating FGF21 expression and then activating the PI3K/AKT pathway. This suggests that HDAC6 may serve as a novel therapeutic target for treating UA-induced endothelial dysfunction.

Background Microplastic has become a kind of pollutant widely existing in soil, atmosphere, fresh water and marine environment. At present, microplastics have been found in many tissues and organs of organisms. Research shows that as a new environmental pollutant, microplastics has shown a health hazard to human and animal. Aging and aging-related diseases are major social and medical problems facing the world. However, up to now, the effect of microplastic exposure on premature aging of blood vessels has not been evaluated. Therefore, we investigated the health damage of microplastics to blood vessels in vivo and in vitro experiments. Methods ELISA, indirect immunofluorescence, SiRNA, laser confocal microscopy, and Flow cytometry were performed to evaluate the effect of microplastics on premature aging of blood vessels. Results In vitro experiments, we found that microplastics can internalize into vascular cells, and the internalized microplastics cause damage to organelles. Further biochemical experiments showed that microplastics stimulation caused the premature aging of blood vessels by detecting a series of aging markers. Further mechanism research indicates that microplastics could increase ROS level of mitochondria mediated by calcium overload, and then ROS leads to the LaminA degradation by CDK5 mediation, further resulting in genomic instability, thus finally causing the aging of vascular cells/tissues. In vivo model, we found that microplastics induced aging damage on vascular tissue, the expression of aging maker molecules were significantly increased. Furthermore, the level of inflammation and oxidative stress was also significantly increased. Conclusion In summary, in this work, we evaluated the effect of microplastic exposure on premature aging of blood vessels, and we also revealed the molecular mechanism by which microplastics cause premature aging of the cardiovascular system.