Fibroblast growth factor 21 inhibits vascular calcification by ameliorating oxidative stress of vascular smooth muscle cells.

Biochemical and biophysical research communications(2023)

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Abstract
Vascular calcification is very common in clinical. Severe vascular calcification is related to the occurrence of adverse events. Oxidative stress (OS) plays a pathophysiological role in the formation of vascular calcification. Previous studies have demonstrated that fibroblast growth factor 21(FGF21) could inhibit vascular calcification both in vivo and in vitro. FGF21 has also been proved to promote the recovery of superoxide dismutase (SOD) and thereby alleviate OS. Thus, our assumption was that FGF21 inhibit vascular calcification partly by restoring the level of antioxidant SOD and reducing OS. In this study, we established the vascular calcification by 5/6 nephrectomy plus high phosphate diet chronic kidney disease (CKD) model. The results showed the receptor of FGF21, fibroblast growth factor receptor 1 (FGFR1) and βKlotho in the aorta increased in CKD group, and mainly located in the media of the artery. Ulteriorly, immunofluorescence (IF) and IHC staining showed that FGFR1 and βKlotho mainly existed in arterial vascular smooth muscle cells (VSMCs). When FGF21 was knock out, the calcification was more severe in FGF21 KO + CKD mice, compared to wild type (WT)+ CKD mice. The transcriptional level of vascular calcification-related genes was significantly higher in FGF21 KO mice than control group. The dihydroethidium (DHE) staining reactive oxygen species (ROS) level in the CKD group was higher compared to the control group, but lower in FGF21 KO + CKD group, and the transcriptional level of SOD1 and SOD2 in FGF21 KO + CKD group was significantly higher than that in CKD group. In conclusion, FGF21 could inhibit vascular calcification, partly by restoring the level of antioxidant SOD and reducing vascular oxidative stress. This study provides further evidence for FGF21 as a candidate drug for cardiovascular protective agents.
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Key words
Fibroblast growth factor 21,Oxidative stress,Vascular calcification
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