title: Losartan Attenuates Myocardial Endothelial-To-Mesenchymal Transition in Spontaneous Hypertensive Rats via Inhibiting TGF-β/Smad Signaling.
abstract: Losartan plays an important role in the inhibition of myocardial fibrosis. But the underlying mechanism is not entirely clear. Emerging evidences have indicated that endothelial-to-mesenchymal transition (EndMT) plays a crucial role in cardiac fibrosis. Here the present study aims to first investigated the effect of Losartan on EndMT in cardiac fibrosis of spontaneous hypertensive rats (SHRs).
  
  
  
  Male SHRs were randomly divided into three groups and fed for 12 weeks, namely the SHR group (Group S), the Losartan-treated group (Group L) and the Prazosin-treated group (Group P). Wistar-Kyoto rats served as controls (Group W). The histological changes were evaluated by Masson's trichrome. Co-expression of CD31 and fibroblast-specific protein 1 (FSP1) were used as the markers of EndMT through immunofluorescence. The expressions of FSP1, CD31, TGF-β, Smad were detected by Western blot analysis.
  
  
  
  It was identified that elevated blood pressure induced a significant increase in myocardial fibrosis and EndMT in SHRs, which was reversed by Losartan and Prazosin treatment. Furthermore, the activity of TGF-β/Smad signaling was detected in the four groups. TGF-β/Smad signaling was activated in SHRs and suppressed by Losartan or Prazosin treatment. Losartan exhibited more efficiently than Prazosin in inhibiting TGF-β/Smad signaling activation, EndMT and myocardial fibrosis.
  
  
  
  These results showed that EndMT played an important role in promoting hypertensive cardiac fibrosis, and that losartan could suppress cardiac fibrosis through the inhibition of EndMT via classical TGF-β/Smad pathway.
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Xiangya Road No.88, Changsha, P.R. China.|Department of Cardiology, Haikou People's Hospital, People's Road No.43, Haikou, Hainan, P. R. China.
authors.forename: Miao
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Emergency, Second Xiangya Hospital, Central South University, Middle Ren-Min Road No. 139, Changsha, P.R. China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Xiangya Road No.88, Changsha, P.R. China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Zu
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Xiangya Road No.88, Changsha, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Cardiology, Haikou People's Hospital, People's Road No.43, Haikou, Hainan, P. R. China.
authors.forename: Shijuan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Haikou People's Hospital, People's Road No.43, Haikou, Hainan, P. R. China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, Xiangya Hospital, Central South University, Xiangya Road No.88, Changsha, P.R. China.
authors.forename: Saidan
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004562:Electrocardiography; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008648:Mesoderm / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D013194:Staining and Labeling; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D024042:Collagen Type I; C579666:FSP1 protein, rat; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D019808:Losartan