Hepatocyte growth factor and basic fibroblast growth factor regulate atrial fibrosis in patients with atrial fibrillation and rheumatic heart disease via the mitogen-activated protein kinase signaling pathway.
The aim of this study was to investigate the interrelation between basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF) and atrial fibrosis in patients with atrial fibrillation (AF) and rheumatic heart disease (RHD), and to explore the possible molecular mechanisms underlying this interrelation. Twenty patients with RHD who were scheduled for valve replacement were divided into two groups, comprising 10 cases with AF and 10 cases with sinus rhythm (SR). Clinical data were collected and a small sample of aseptic left atrial appendage was collected by the surgeon. Hematoxylin and eosin (H&E) and Masson's trichrome-stained sections were used to evaluate the cross-sectional area and level of fibrosis, respectively. The expression levels of bFGF and HGF were assessed using immunohistochemistry. The phosphorylation levels of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MEK1/2), c-Jun N-terminal kinase 1/2 (JNK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 in atrial tissue were measured using western blotting. Compared with the SR group, myocardial cell diameter was significantly expanded and there was increased collagen deposition in the AF group (P<0.05). The distribution of bFGF in the AF group was significantly higher than that in the SR group (P<0.05); however, HGF levels were significantly lower in the AF group (P<0.05). The phosphorylation levels of MEK1/2, ERK1/2, JNK1/2 and p38 in the AF group were significantly higher than those in the SR group (P<0.05). The results indicated that bFGF may promote the development of atrial fibrosis, while HGF may function in an opposite manner in patients with AF and RHD. The mitogen-activated protein kinase (MAPK) signaling pathway may be the molecular basis for these roles in atrial fibrosis.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mingjiang
M
Li
Xin
X
Yi
Lele
L
Ma
Yanli
Y
Zhou
atrial fibrosis; basic fibroblast growth factor; hepatocyte growth factor; mitogen-activated protein kinase signaling pathway; rheumatic heart disease