| Objective The study examines cell proliferation, expression ofα-SMA mRNA and protein, production of Connective tissue growth factor(CTGF) mRNA and protein, and secretion of collagen and gelatinase,through interventing human atrial fibroblast in vitro with hepatocyte growth factor(HGF)and transforming growth factor-β1 (TGFβ1),to first observe the relationship between the incidence and maintaining of atrial fibrillation (AF) and positive and negative control of TGFβ1 and HGF on atrial fibrosis of rheumatic heart disease.Methods The study included 10 Sinus rhythm(SR) and 10 Chronic atrial Fibrillation (CAF) patients of accepting surgery; then got aseptic right atrial appendage organizations to rear human atrial fibroblast and intervent cells with HGF and TGFβ1, and examined cell proliferation by WST-1, mRNA content of collagen I, gelatinase (MMP-2),TIMP-2,TGFβ1,CTGF andα-SMA by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), protein expression of CTGF andα-SMA by immunofluorescence and Western-Blot.Results (1) Human atrial fibroblasts were isolated and cultured successfully in vitro and identified by immunofluorescence.(2) TGFβ1 can promote cell proliferation of human atrial fibroblasts in a dose and time dependent manner,the action was most significant with concentration of 10ng/ml after 48 hours. HGF can inhibit cell proliferation of human atrial fibroblasts in a dose and time dependent manner, the action was the most significant with concentration of 100ng/ml after 48 hours. (3)Compared with SR group, left atrium was dilatated significantly in CAF group.In CAF group atrial fibroblasts,mRNA content of collagen I, MMP-2,TGFβ1,CTGF andα-SMA were increased significantly;mRNA content of TIMP-2 was decreased significantly. mRNA content of collagen I and MMP-2 were positively correlated with LAD and AF duration;mRNA content of TGFβ1,CTGF andα-SMA were positively correlated with mRNA content of collagen I and MMP-2;mRNA content of MMP-2 were negatively correlated with mRNA content of TIMP-2.(4)Compared with SR group, the expression of mRNA and protein of CTGF andα-SMA in CAF atrial fibroblasts were increased significantly;protein content of CTGF was positively correlated with protein content ofα-SMA, and negatively correlated with LAD and AF duration.(5)In CAF atrial fibroblasts,TGFβ1 promoted mRNA expression of collagen I, MMP-2,CTGF,α-SMA and protein expression of CTGF andα-SMA. TGFβ1 inhibited mRNA expression of TIMP-2. However,the action of HGF was just opposite.(6)In CAF atrial fibroblasts,HGF inhibited mRNA expression of TGFβ1, HGF could inhibit the role of TGFβ1 partly because of inhibiting the expression of CTGF.Conclusions Increasing expression of TGFβ1 and CTGF in AF atrial fibroblasts could promote the secretion of collagen I, MMP-2andα-SMA;and cause reconstruction of atria,which was related with the incidence and maintaining of AF.TGFβ1 and HGF could respectively promote and inhibit proliferation of atrial fibroblast;expression of CTGF,α-SMA; secretion of collagen I ,MMP-2;and atrial fibrosis. HGF could inhibit the role of TGFβ1 partly because of inhibiting the expression of CTGF.
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