title: Valsartan blocks thrombospondin/transforming growth factor/Smads to inhibit aortic remodeling in diabetic rats.
abstract: BACKGROUND
  Angiotensin II (Ang II) and transforming growth factor β (TGFβ) are closely involved in the pathogenesis of diabetic complications. We aimed to determine whether an aberrant thrombospondin 1 (TSP1)-mediated TGFβ1/Smads signaling pathway specifically affects vascular fibrosis in diabetic rats and whether valsartan, an Ang II subtype 1 receptor blocker, has an anti-fibrotic effect.
  
  
  METHODS
  Age-matched male Wistar rats were randomly divided into 3 groups: control (n = 8), diabetes (n = 16) and valsartan (30 mg/kg/day) (n = 16). Type 2 diabetes mellitus (T2DM) was induced by a high-calorie diet and streptozotocin injection. Morphological and biomechanical properties of the thoracic aorta were assessed by echocardiography and cardiac catheterization. Masson staining was used for histological evaluation of extracellular matrix (ECM). The expression of components in the TSP1-mediated TGFβ1/Smads signaling pathway was analyzed by immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction.
  
  
  RESULTS
  As compared with controls, diabetic aortas showed reduced distensibility and compliance, with excess ECM deposition. Components in the TSP1-mediated TGFβ1/Smads signaling pathway, including TSP1, TGFβ1, TGFβ type II receptor (TβRII), Smad2 and Smad3, were accumulated in vascular smooth muscle cytoplasm of diabetic aortas and their protein and mRNA levels were upregulated. All these abnormalities were attenuated by valsartan.
  
  
  CONCLUSIONS
  TSP1-mediated TGFβ1/Smads pathway activation plays an important role in marcovascular remodeling in T2DM in rat. Valsartan can block the pathway and ameliorate vascular fibrosis.
  The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1053842818141195.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. sunhuisasa303@sohu.com.|Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China. sunhuisasa303@sohu.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Geriatric Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. zhaoyong600@sohu.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. xixiuping2@sohu.com.|Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China. xixiuping2@sohu.com.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Bi
authors.affiliation: Department of Geriatric Cardiology, Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. lishaohua2@sohu.com.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Cardiology, Jinan Central Hospital Affiliated to Shandong University, Jinan, 250013, China. suguohai2@sohu.com.
authors.forename: Guohai
authors.initials: G
authors.lastname: Su
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. miaoya3@sohu.com.
authors.forename: Ya
authors.initials: Y
authors.lastname: Miao
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. maxiaomaxiao2@sohu.com.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. zhangyunzhang2@sohu.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. zhangweizhang2@sohu.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, the Department of Cardiology, Shandong University, Qilu Hospital, No.107, Wen Hua Xi Road, Jinan, Shandong Province, 250012, China. zhongming2@medmail.com.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhong
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D005355:Fibrosis; D008297:Male; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013311:Streptozocin; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D000068756:Valsartan / Q000494:pharmacology*; D066253:Vascular Remodeling / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D051785:Smad Proteins; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; C582391:Thbs1 protein, rat; D013311:Streptozocin; D000068756:Valsartan