title: Periostin as a novel factor responsible for ventricular dilation.
abstract: BACKGROUND
  Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart.
  
  
  RESULTS
  Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV dP/dt(max), and LV dP/dt(min) at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunction such as brain natriuretic peptide and endothelin-1 gene expression were significantly increased after transfection in the LV of rats transfected with the periostin gene. These data demonstrate that overexpression of the periostin gene led to cardiac dysfunction. Thus, we examined the inhibition of periostin in Dahl salt-sensitive rats by an antisense strategy because periostin is highly expressed in heart failure. Importantly, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of LV function.
  
  
  CONCLUSIONS
  The present study demonstrates the contribution of the periostin gene to cardiac dilation in animal models. Inhibition of periostin might become a new therapeutic target for the treatment of heart failure.
authors.affiliation: Daiichi Suntory Biomedical Research Ltd, 1-1-1 Wakayamadai Shimamoto-cho, Mishima-gun, Osaka, Japan.
authors.forename: Naruto
authors.initials: N
authors.lastname: Katsuragi
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Noriko
authors.initials: N
authors.lastname: Nakamura
authors.forename: Tayehito
authors.initials: T
authors.lastname: Ochiai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Kayoko
authors.initials: K
authors.lastname: Kawashima
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kaneda
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Keijiro
authors.initials: K
authors.lastname: Sugimura
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000648:ultrastructure; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018411:Spodoptera; D014162:Transfection; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D005353:Fibronectins; D020319:Oligodeoxyribonucleotides, Antisense; C512836:Postn protein, rat; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins