The role of FGF21 in the pathogenesis of cardiovascular disease

Abstract

The morbidity and mortality of cardiovascular diseases (CVDs) are increasing worldwide and seriously threaten human life and health. Fibroblast growth factor 21 (FGF21), a metabolic regulator, regulates glucose and lipid metabolism and may exert beneficial effects on the cardiovascular system. In recent years, FGF21 has been found to act directly on the cardiovascular system and may be used as an early biomarker of CVDs. The present review highlights the recent progress in understanding the relationship between FGF21 and CVDs including coronary heart disease, myocardial ischemia, cardiomyopathy, and heart failure and also explores the related mechanism of the cardioprotective effect of FGF21. FGF21 plays an important role in the prediction, treatment, and improvement of prognosis in CVDs. This cardioprotective effect of FGF21 may be achieved by preventing endothelial dysfunction and lipid accumulating, inhibiting cardiomyocyte apoptosis and regulating the associated oxidative stress, inflammation and autophagy. In conclusion, FGF21 is a promising target for the treatment of CVDs, however, its clinical application requires further clarification of the precise role of FGF21 in CVDs.

Figure 1

Pathophysiological changes of cardiovascular diseases and the role of FGF21 in these processes.

Figure 2

FGF21 induces protective effect on cardiovascular diseases through multiple signaling pathways. ABCA1: ATP-binding cassette transporter A1; ABCG1: ATP-binding cassette transporter G1; ACC: Acetyl-CoA carboxylase; Akt: Protein kinase B; AMPK: AMP-activated protein kinase; ARE: Antioxidant responsive element; BAD: B-cell lymphoma 2-associated death promoter; Bax: B-cell lymphoma 2-associated X protein; Bcl: B-cell lymphoma; CPT: Carnitine palmitoyltransferase; DCM: Diabetic cardiomyopathy; eNOS: Endothelial nitric oxide synthase; FATP: Fatty acid transport protein; GSK: Glycogen synthase kinase; HDL-C: High-density lipoprotein cholesterol; IL: Interleukin; LDL-C: Low-density lipoprotein cholesterol; MI: Myocardial infarction; NF: Nuclear factor; NLRP3: NOD-like receptor protein 3; NO: Nitric oxide; Nrf2: Transcription factor-E2-related factor 2; PGC: Peroxisome proliferator-activated receptor-γ coactivator; PI3K: Phosphatidylinositol-3-kinase; SIRT1: Sirtuin 1; SOD: Superoxide dismutase; TC: Total cholesterol; TG: Triglyceride; TNF: Tumor necrosis factor; UCP: Uncoupling protein; Vps34: Vacuolar protein sorting 34.