title: Lentivirus mediated IL-17R blockade improves diastolic cardiac function in spontaneously hypertensive rats.
abstract: BACKGROUND
  Hypertension causes cardiac fibrosis characterized by low-grade inflammation. We hypothesized that proinflammatory cytokine, interleukin-17 (IL-17) is important in hypertensive cardiac fibrosis. The pre-ligand assembly domain (PLAD) of IL-17 receptor A (IL-17RA) mediates receptor-chain associations essential for signaling. This study was designed to explore the role of IL-17 RA PLAD in hypertension-induced cardiac fibrosis.
  
  
  METHODS
  Eight-week-old male spontaneously hypertensive rats (SHRs) were divided into 2 groups, depending on receiving IL-17RA PLAD-Ig or green fluorescent protein (GFP) lentivirus. Age-matched Wistar Kyoto rats served as controls. Cardiac function was determined by echocardiography. Cardiac hypertrophy and fibrosis were histopathologically examined. Matrix metalloproteinase (MMP) and tissue inhibitors of metalloproteinase (TIMP) expression were quantified by immunoblotting. Collagen content was quantified.
  
  
  RESULTS
  Both cardiac systolic and diastolic function and myocardial fibrosis in SHRs was improved significantly by the IL-17RA PLAD. Expression of MMP-2 and MMP-9, TIMP-1 and -2, type I and type III collagen were statistically decreased by IL-17RA PLAD-Ig treatment. Collagen quantitation, as well as collagen concentration and collagen cross-linking, were reduced by IL-17/IL-17R signal blockade.
  
  
  CONCLUSIONS
  IL-17/IL-17RA signaling plays an important role in myocardial collagen metabolism in hypertension-induced diastolic dysfunction.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Xueting
authors.initials: X
authors.lastname: Wang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Feng
authors.forename: Shuqing
authors.initials: S
authors.lastname: Li
authors.forename: Wendan
authors.initials: W
authors.lastname: Tian
authors.forename: Tengfei
authors.initials: T
authors.lastname: Xu
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Song
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004562:Electrocardiography; D005355:Fibrosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000517:prevention & control; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D020381:Interleukin-17 / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D053722:Receptors, Interleukin-17 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D014162:Transfection
chemical_list: D024061:Collagen Type III; C109985:IL17RA protein, human; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases