TMAO Affects Proliferation Of Cardiac Fibroblasts Via PI₃K/AKT/mTOR Signaling Pathway

Objective To investigate the mechanism of TMAO affecting the proliferation of fibroblasts in the heart through PI₃K/AKT/mTOR signaling pathway.Method cardiac fibroblasts were cultured in medium containing 0,0.5,1,2.5,5,10,25,50?mol/L TMAO for 48 hours as the concentration gradient group;Cardiac fibroblasts were treated with TMAO for 0,15,30,60 min as the time gradient group;before treated with TMAO,treat cells with LY294002?PI₃K inhibitor?in advance for 30 minutes,as the inhibitor group.The protein expression was detected by western blot,MTT assay was used to detect the proliferation of cells.Results When cell viability was measured by MTT colorimetry,D?490?of TMAO treatment group increased in a concentration-dependent manner,and reached the highest level at 10?mol/L.TMAO increased the expression of p-PI₃K,p-AKT and p-mTOR in PI₃K/AKT/mTOR cell proliferation signaling pathway.p-PI₃K was highest in TMAO at 10?mol/L and treated for 30 min,The expression level of p-AKT and p-mTOR was the highest when they were treated with TMAO at 25?mol/L and for 60 min.In the inhibitor group,the expression levels of p-PI₃K,p-AKT,and p-mTOR were significantly reduced in the group treated with the PI₃K inhibitor as compared with the cells treated with TMAO alone.The results were statistically significant compared with the control group?P<0.05?.Conclusion TMAO promotes the proliferation of cardiac fibroblasts and activates the PI₃K/AKT/mTOR signaling pathway.