title: Left ventricular periostin gene expression is associated with fibrogenesis in experimental renal insufficiency.
abstract: BACKGROUND
  Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown.
  
  
  METHODS
  Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats.
  
  
  RESULTS
  CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions.
  
  
  CONCLUSIONS
  Periostin is involved in fibrotic cardiac remodelling in CRI. The re-expression of periostin is localized to the fibrotic and inflammatory lesions and is most likely the consequence of elevated BP.
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Biocentre Oulu, Oulu, Finland.
authors.forename: Virva
authors.initials: V
authors.lastname: Pohjolainen
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.forename: Juha
authors.initials: J
authors.lastname: Näpänkangas
authors.forename: Peeter
authors.initials: P
authors.lastname: Kööbi
authors.forename: Arttu
authors.initials: A
authors.lastname: Eräranta
authors.forename: Mika
authors.initials: M
authors.lastname: Ilves
authors.forename: Raisa
authors.initials: R
authors.lastname: Serpi
authors.forename: Ilkka
authors.initials: I
authors.lastname: Pörsti
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D002114:Calcinosis; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000494:pharmacology; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006352:Heart Ventricles / Q000378:metabolism*; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D007677:Kidney Function Tests; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009392:Nephrectomy / Q000009:adverse effects; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051437:Renal Insufficiency / Q000150:complications / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D015815:Cell Adhesion Molecules; D004872:Ergocalciferols; C512836:Postn protein, rat; D012333:RNA, Messenger; C084656:paricalcitol