Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown. In this study, apoE(-/-) mice were fed an atherogenic diet for 4 weeks with and without subcutaneous injections of FGF-21. ApoE(-/-) mice fed an atherogenic diet showed hyperlipidemia, a large plaque area in aortas and increased vessel wall thickness. Plasma FGF-21 content and protein level of FGF receptor 1 (FGFR1) in aortas was greater in apoE(-/-) than C57BL/6J mice. Exogenous FGF-21 treatment significantly ameliorated dyslipidemia in apoE(-/-) mice. FGF-21-treated apoE(-/-) mice showed reduced number of aortic plaques and plaque area as well as reduced number of TUNEL-positive cells. Protein levels of the endoplasmic reticulum stress markers glucose-regulated protein 94, caspase-12 and C/EBP homologous protein were reduced by 34.5, 31.4 and 26.5 %, respectively, in apoE(-/-) mice. Endogenous expression of FGF-21 and its receptor FGFR1 were upregulated in apoE(-/-) mice, and exogenous administration of FGF-21 ameliorated the atherogenic-induced dyslipidemia and vascular atherosclerotic lesions. FGF-21 protecting against atherosclerosis might be in part by its inhibitory effects on endoplasmic reticulum stress-mediated apoptosis.

Fibroblast growth factor 21 (FGF21), a hormone with multiple metabolic properties, has proven to be pleiotropic biological effects and may play pivotal role in numerous cardiovascular and metabolic diseases in the future. Vascular calcification (VC) is a concomitant pathological process of various cardiovascular and metabolic diseases. However, the effects of FGF21 on VC remain unclear. Therefore, in this research, we aimed to explore the roles and mechanisms of FGF21 in VC induced by vitamin D3 plus nicotine (VDN) treatment rats. After 28 days VDN treatment, the calcium overload was confirmed by blood pressure, ultrasound imaging, calcium content, ALP activity and aortic pathological characteristics. In terms of FGF21, exogenous FGF21 can ameliorate the elevation of blood pressure, aortic calcification and related injury in VC rats. To investigate the mechanisms of FGF21 on VC, the endoplasmic reticulum stress (ERS) mediated apoptosis pathways were tested. As a method to detect apoptosis, the increased positive TUNEL staining cells were alleviated by FGF21 treatment. Furthermore, exogenous FGF21 can suppress the increased ERS chaperone, GRP78, in the calcified aortas. In the three pathways of ERS mediated apoptosis, we found CHOP pathway and caspase-12 pathway were involved in the treatment of FGF21, but not p-JNK/JNK pathway. Our study proved for the first time that FGF21 can inhibit the progress of VC by alleviating ERS mediated apoptosis in rats. FGF21 might be a new target for preventing and treating VC.

A highly efficient non-noble metal catalytic system for selective transfer hydrogenation of an α,β-unsaturated aldehyde without use of alkaline additives was developed.