Abstract
BackgroundFGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Despite intensive study of the metabolic functions of FGF21, its important role in heart disease needs further exploration. Apoptosis induced by ox-LDL in vascular endothelial cells is an important step in the progress of atherosclerosis.MethodsThe effects of FGF21 treatment on apoptosis induced by ox-LDL were tested in HUVECs. The role of FGF21 in atherosclerosis was studied by evaluating its function in apolipoprotein E double knockout (apoE−/−) mice.ResultsWe found that apoptosis in HUVECs was alleviated by FGF21 treatment. The effects of FGF21 were independent of the ERK1/2 pathway and were mediated through inhibition of the Fas signaling pathway. FGF21 suppressed the development of atherosclerosis, and the administration of FGF21 ameliorated Fas-mediated apoptosis in apoE−/− mice.ConclusionFGF21 protects against apoptosis in HUVECs by suppressing the expression of Fas; furthermore, FGF21 alleviated atherosclerosis by ameliorating Fas-mediated apoptosis in apoE−/− mice.
Highlights
Fibroblast growth factor 21 (FGF21) is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism
When Human umbilical vein endothelial cells (HUVECs) were incubated with FGF21, apoptosis induced by ox-Low-density lipoprotein (LDL) intake in these cells was reduced significantly (Fig. 1a, b)
These results suggest that FGF21 inhibits HUVEC apoptosis
Summary
FGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Recombinant FGF21 as a therapeutic intervention was Recently, it was demonstrated that the levels of FGF21 in circulation are promoted in CHD [11] and that FGF21 could attenuate pathological heart remodeling in myocardial infarction [12]. Basic on those studies, FGF21 was suggested to be related to arteriosclerosis, but the effect of FGF21 is still not clear in atherosclerosis, an inflammatory disease that is related to metabolic disorders. Preliminary clinical studies reported that serum FGF21 levels were increased in patients with atherosclerosis and in patients with a high risk of atherosclerosis [13]
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