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Losartan prevents aortic dissection via downregulating TGF-β/SMADs pathway in Sprague Dawley rats

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摘要 Background Aortic dissection(AD)is a lethal medical emergency,which lacks specific biomarkers and effective pharmaceutical therapies.Increasing evidences have shown beneficial effect of angiotensin receptor blocker(ARB)drugs on downregulating transforming growth factor-β(TGF-β)pathway in Marfanoid AD.However,for non-Marfanoid AD,the effectiveness of ARB drugs,as well as the possible mechanisms,remains unclear.Methods Sprague Dawley(SD)rats were fed by gavage(i.g.)with either 150 mg/(kg·d)Hydroxyethyl diamine(AEEA)or isovolumic saline(normal saline group).AEEA-induced SD rats were further randomly divided into three groups,including the AEEA+Losartan group[AEEA induction+20 mg/(kg·d)i.g.Losartan],the AEEA+Amlodipine group[AEEA induction+6.5 mg/(kg·d)i.g.Amlodipine]and the AEEA+normal saline group(AEEA induction+isovolumic saline i.g.)group.Thus there were 4 groups with 12 mice in each.Tail blood pressure,aortic diameter and the number of aortic dissected lesions were measured in the above 4 groups 4 weeks thereafter.Western-blot was used to detect the expression of components of TGF-β/SMADs pathway,such as TGF-β1,drosophila mothers against decapentaplegic protein 2(Smad2),Smad3,Smad4,protein kinase B(AKT)and phosphorylated AKT(p-AKT).Results No significant difference of blood pressure was seen between the AEEA+Losartan group and the AEEA+Amlodipine group(P=0.81).Ultrasound data indicated a significant reduction in aortic dilation of ascending aorta,aortic arch and descending aorta in Losartan intervention group relative to the Amlodipine intervention group(P<0.001).Hematoxylin-eosin(HE)staining of aortic tissue demonstrated that under the setting of AEEA induction,AEEA+Losartan group had a lower incidence of aortic dissection than the AEEA+normal saline group and the AEEA+Amlodipine group(all P<0.01).Losartan significantly reduced the expression of TGF-β1,Smad2,Smad3,Smad4 in aortic tissues of AEEA-induced rats(all P<0.05).Conclusions Independent of BP reduction,Losartan,as an ARB drug,can prevent aortic dissection by inhibiting TGF-β/SMADs signaling pathway.
作者 HUANG Cheng DING Zhao-hui JIANG Zhi-sheng HUANG Wen-hui 黄澄;丁兆慧;姜志胜;黄文晖(Department of Cardiology, Guangdong Cardiovascular institute, Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences;Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, Hengyang Medical School, University of South China)
出处 《South China Journal of Cardiology》 CAS 2020年第4期269-276,共8页 岭南心血管病杂志(英文版)
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