Effects Of Valsartan, A Type 1 Angiotensin â…¡ Receptor Antagonist, On Airway Smooth Muscle Cells Proliferation

Background:Asthma is a chronic disease of seriously threathening global publichealth. Although the past 10 years we have rapid developments on recognition anddiagnosis,its morbidity and mortality rate is increasing, patients of asthma hasreached 300 million. Substantial pathological studies confirmed that there are bothinflammatory cell infiltration and airway remodeling characterizing byinflammatory cell infiltration, airway smooth muscle cell hypertrophy andhyperplasia, basement menbrance thickness within the bronchial wall of asthmaticpatients [1]. This change not only appeared in the asthmatic later period, but earlyin the asthma.One of the features that is very imporment in this respect is airwaysmooth muscle cell proliferation. It may be considered to an importantpathological basis of refractory asthma, and closely relating airwayhyperresponsiveness and drug efficacy.In recent years, It has been reported that angiotensin II and type 1 angiotensinII receptor may be involved in airway remodeling[2,3],the mechanism of which isnot yet clear.This article is designed to study angiotensin II and type 1 angiotensinII receptor antagonist on airway smooth muscle cells proliferation and observedthe expression ATR and TGF-β1mRNA,also the action and mechanism ofangiotensin II and its receptor in the cellular level.Objective :To investigate the effect of type 1 angiotensin II receptor antagoniston airway smooth muscle cells proliferation. Methods: Human airway smooth muscle cells (HASMCs) derived from humanbronchus were cultured and stimulated with or without valsartan and angiotensinII in vitro.The survival rate of HASMCs was detected by MTT method. Cell cyclewas detected by flow cytometry.Realtime. PCR was explored to measure themRNA expression levels of angiotensin II receptor and transforming growth factor–β1(TGF-β1). The levels ofAT1R,AT2Rprotein were analyzed by western blot.Results:⑴The proliferation rate of HASMCs was increased significantly in AngII group,compared with control group(P<0.05);valsartan, a type 1 angiotensin IIreceptor antagonist,decreased the proliferation rate of cells stimulated by Ang II(P<0.05).⑵Flow cytometry disclosed that the Ang II significantly increased Sphase of HASMCs (P<0.05); valsartan decreased S phase of cells stimulated byAng II (P<0.05).⑶The expression of AT1R,AT2R in theAng II group were higherthan the control group(P<0.05) , AT1R of valsartan + Ang II group(P<0.05)werelower then. the Ang II group ,but AT2R was not significant difference;[4]Theexpression of TGF-β1mRNA in the Ang II group were higher than the controlgroup(P<0.05) and valsartan +Ang II group(P<0.05).Conclusions: Type 1 angiotensin II receptor antagonist may inhibit theproliferation of HASMCs by suppressingAT1R and downregulating of TGF-β1.