Abstract
Background: Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) as an adipocytokines is a new hypoglycemic strategy and is inversely related to bone mineral density.Methods: To evaluate the contribution of FGF21 to VC in HD patients, we preliminary sreened 802 HD patients of two large HD centers in China. At last 388 HD patients were entered this cross-sectional study. We detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the three segments of thoracic aorta (TA), including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our 388 HD patients. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro.Results: The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1) and Ln(DTACS+1) respectively in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 combined with age, calcium and intact parathyroid hormone demonstrated a high area under the curve (AUC=0.84) with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition (EndMT).Conclusions: Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.Trial registration Chinese Clinical Trial Registry, identifier: ChiCTR1900028249. Registered 16 December 2019-Retrospectively registered,http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=5981
Fibroblast Growth Factor 21 Attenuates Vascular Calcification by Alleviating Endoplasmic Reticulum Stress Mediated Apoptosis in Rats
