Losartan prevents aortic dissection via downregulating TGF-β/SMADs pathway in Sprague Dawley rats
HUANG Cheng1
DING Zhao-hui1
JIANG Zhi-sheng2
HUANG Wen-hui1
1.Department of Cardiology, Guangdong Cardiovascu-lar institute, Provincial Key Laboratory of Coronary Heart Dis-ease Prevention, Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences, Guangzhou 510080, Guangdong, China2.Institute of Cardiovascular Dis-ease and Key Laboratory for Arteriosclerology of Hunan Prov-ince, Hengyang Medical School, University of South China,Hengyang 421000, Hunan, China
摘要：Background Aortic dissection(AD)is a lethal medical emergency,which lacks specific biomarkers and ef-fective pharmaceutical therapies.Increasing evidences have shown beneficial effect of angiotensin receptor block-er(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 pres-sure,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 reduc-tion 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).Conclu-sions Independent of BP reduction,Losartan,as an ARB drug,can prevent aortic dissection by inhibiting TGF-p/SMADs signaling pathway.
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论文发表日期：2020-12-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 269-276 )
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