Role Of FGF21 On Proliferation And Collagen Synthesis Of Cardiac Fibroblasts And Expression Of FGF21 In Myocardial Tissues Of Rheumatic Patients With Atrial Fibrillation

Part I Role of FGF21 on cardiac fibroblasts proliferation and phenotypic transformation induced by TGF-?1Objective To explore the role of fibroblast growth factor21 (FGF21) on cardiac fibroblasts proliferation and phenotypic transformation induced by transforming growth factor-beta 1 (TGF-?1).Methods It is divided into blank control group, TGF-?1 group, FGF21 group, TGF-?1+FGF21 group in this part of the experiment. After cardiac fibroblasts induced by different incentive to the scheduled time, CCK8 assay was used for detecting cardiac fibroblasts proliferation of each group, immunofluorescence staining was used to observe the expression of cardiac fibroblasts marker--a-smooth muscle actin (a-SMA), real-time quantitative PCR was used to detect the mRNA levels of cell proliferation markers including PCNA and Ki67.Results Compared with the blank control group, TGF-?1 can significantly increase the cardiac fibroblasts proliferation rate, and the mRNA contents of cell proliferation markers PCNA and Ki67 were also significantly increased. And TGF-?1 can significantly increase the expression of cardiac fibroblasts marker a-SMA.However, FGF21 significantly inhibited cardiac fibroblasts proliferation and cardiac fibroblasts transfer to cardiac muscle of fibroblasts induced by TGF-?1.Conclusion FGF21 could repress cardiac fibroblasts proliferation and phenotypic transformation induced by TGF-?1.Part ? Role of FGF21 on collagen synthesis of cardiac fibroblasts induced by TGF-?1Objective To explore role of fibroblast growth factor 21 (FGF21) on collagen synthesis of cardiac fibroblasts induced by transforming growth factor-beta 1 (TGF-?1).Methods It is divided into blank control group, TGF-?1 group, FGF21 group, TGF-?1+FGF21 group in this part of the experiment. After cardiac fibroblasts induced by different incentive to the scheduled time, real-time quantitative PCR was used to detect the mRNA levels of myocardial fibrosis markers including CTGF, Collagen ? and Collagen ?. In addition, Western Blot was used to detect protein expression levels of Collagen I and Collagen ?.Results Compared with the blank control group, TGF-?1 can significantly increase the mRNA contents of myocardial fibrosis markers including CTGF, Collagen I and Collagen ?. And TGF-?1 can significantly increase the protein expression of Collagen ? and Collagen ?. However, FGF21 significantly inhibited mRNA levels and preotein expression of myocardial fibrosis markers induced by TGF-?1.Conclusion FGF21 could repress collagen synthesis of cardiac fibroblasts induced by TGF-?1.Part ? Expression of FGF21 in myocardial tissue of rheumatic heart disease patients with atrial fibrillationObjective To explore the relationship of FGF21 and atrial fibrosis of rheumatic heart disease patients with atrial fibrillation, we detected serum and cardiac expression of FGF21 in rheumatic heart disease patients.Methods Rheumatic heart disease patients were divided into sinus rhythm group and atrial fibrillation group, and serum and myocardial tissue were collected in the surgery of valve replacement. HE pathological staining was used to observe cross-sectional area of cardiomyocytes in each group, Masson staining and mRNA contents of myocardial fibrosis markers including CTGF, Collagen I and Collagen III were used to evaluate atrial fibrosis. In addition, the ELISA kit was used to detect serum level of FGF21 in each group, immunohistochemical staining and real-time quantitative PCR were applied to detect the expression level of FGF21 in atrial tissues. Finally, the linear correlation analysis was used to evaluate the relationship of between FGF21 expression level and the severity of atrial fibrosis of rheumatic heart disease patients.Results Compared with the sinus rhythm group, cross-sectional area of cardiomyocytes, the collagen volume fraction and mRNA levels of myocardial fibrosis markers including CTGF, Collagen ? and Collagen ? were significantly increased in patients with atrial fibrillation group. In addition, the marked increase in serum levels of FGF21 was shown in patients with atrial fibrillation, the immunohistochemical staining showed that FGF21 expression was significantly higher in myocardial tissue of patients with atrial fibrillation, and FGF21 mRNA level was also increased significantly. It was found by linear correlation analysis that the expression level of FGF21 was positively associated with the degree of atrial fibrosis.Conclusion Expression of FGF21 was increased significantly in the serum and myocardial tissue of rheumatic heart disease patients with atrial fibrillation, was closely related to the severity of atrial fibrosis, which might participate in the occurrence and maintaining of atrial fibrillation. Therefore, FGF21 maybe one of the biomarkers as atrial fibrosis in rheumatic heart disease patients with atrial fibrillation.