期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 234, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2022.113410
关键词
PM2.5; Vascular calcification; OPG/RANKL signaling pathway; ROS; Rutin
资金
- National Natural Science Foundation of China [21707085, 31770382]
- Fundamental Research Program of Shanxi Province [20210302124587]
Atmospheric exposure to PM2.5 significantly contributes to the incidence and mortality of cardiovascular disease. This study reveals that PM2.5 promotes vascular calcification by enhancing hydroxyapatite deposition and activating the OPG/RANKL pathway. ROS generation induced by PM2.5 plays a crucial role in this process, and rutin effectively prevents vascular calcification by regulating the OPG/RANKL pathway.
Atmospheric PM2.5 exposure greatly contributes to the incidence of and mortality from cardiovascular disease (CVD). Owing to the crucial role of vascular calcification in the progression of CVD, it is imperative to elucidate the effects of PM2.5 on vascular calcification to understand the toxic mechanisms of haze-induced CVD. However, the effects of PM2.5 exposure on vascular calcification and the underlying molecular mechanisms are still unclear. In this work, the in vitro and in vivo models were used to illuminate the effects of PM2.5 on vascular calcification. We found that PM2.5 promoted the deposition of hydroxyapatite in calcifying vascular cells. Moreover, hydroxyapatite deposition was significantly enhanced by 3.5 times compared with those in the control group in aortas of ApoE(-/-) mice after exposure winter PM2.5 (1.5 mg/kg b.w.), accompanied by activation of the OPG/ RANKL pathway and inflammatory cytokines' expressions. Moreover, PM2.5-induced reactive oxygen species (ROS) generation was observed. NAC, an ROS inhibitor, observably alleviated the promotion effects of PM2.5 on vascular calcification. Furthermore, rutin effectively prevented vascular calcification by regulating the OPG/ RANKL pathway. Our results suggest that PM2.5 play an important role in the occurrence and development of vascular calcification, and that rutin has an antagonistic effect on it.
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