title: Effects of angiotensin II receptor blocker on myocardial endothelial-to-mesenchymal transition in diabetic rats.
abstract: BACKGROUND
  Emerging evidence has indicated that the endothelial-to-mesenchymal transition (EndMT) is a crucial event during early stages of cardiac fibrosis. In the present study, we first investigated the influence of Irbesartan (Irb) on myocardial EndMT in diabetic rats.
  
  
  METHODS
  Diabetic rats were divided into two groups: the diabetic group (DM) and the Irb-treated group (DM+Irb). Wistar-Kyoto rats served as controls. The pathological changes were investigated by microscopy. Immunofluorescence was performed to evaluate the co-expression of CD31 and fibroblast-specific protein 1 (FSP1). FSP1 and α-SMA expressions were detected by RT-PCR and Western blot analysis. EndMT was also studied in human aortic endothelial cells (HAECs) that had been exposed to high glucose (HG) levels.
  
  
  RESULTS
  Increased interstitial fibrosis was detected in the DM group. Double labeling revealed CD31 expression in FSP1-positive cells in the DM group, and this expression was diminished by Irb treatment (P<0.05). In vitro, we found that HG stimulated angiotensin II synthesis in HAECs. When HAECs were exposed to HG, some of the cells acquired a spindle-shaped morphology and demonstrated a loss of CD31 labeling, which was attenuated by Irb treatment. FSP1 and α-SMA mRNA and protein expression levels were markedly upregulated in diabetic rats compared to controls, and their expressions were inhibited by Irb treatment (P<0.05).
  
  
  CONCLUSIONS
  The results provide the novel insight that an angiotensin II receptor blocker might prevent diabetic cardiomyopathy by abrogating EndMT in diabetic rats.
authors.affiliation: Institute of Nephrology, Zhong Da Hospital, Southeast University, Nanjing, China.
authors.forename: Ri-Ning
authors.initials: RN
authors.lastname: Tang
authors.forename: Lin-Li
authors.initials: LL
authors.lastname: Lv
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Zhang
authors.forename: Hou-Yong
authors.initials: HY
authors.lastname: Dai
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
authors.forename: Jie
authors.initials: J
authors.lastname: Ni
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Ma
authors.forename: Bi-Cheng
authors.initials: BC
authors.lastname: Liu
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004452:Echocardiography; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D000077405:Irbesartan; D008297:Male; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D002135:Calcium-Binding Proteins; D017931:DNA Primers; C579666:FSP1 protein, rat; D012333:RNA, Messenger; D013777:Tetrazoles; D000077405:Irbesartan