title: Regulation of cardiac melusin gene expression by hypertrophic stimuli in the rat.
abstract: OBJECTIVE
  Melusin is an integrin β1-interacting protein proposed to act as a biomechanical sensor in the heart. We characterized mechanisms and signalling pathways regulating cardiac melusin expression.
  
  
  METHODS
  Infusion of arginine(8) -vasopressin (AVP) in Sprague-Dawley (SD) rats, spontaneously hypertensive rats (SHR) and double transgenic rats (dTGR) harbouring both human angiotensinogen and renin genes as well as infusion of angiotensin II (Ang II) in SD rats were used. The effect of direct left ventricular (LV) wall stretch was analysed by using isolated perfused rat heart preparation. For the cell culture studies, mouse atrial HL-1 cell line and neonatal rat ventricular myocytes (NRVMs) were used.
  
  
  RESULTS
  Left atrial melusin mRNA levels increased already after 30 min of AVP infusion. Ang II caused significant upregulation of left atrial melusin mRNA (2.1-fold at 6 h, P < 0.05) and protein (1.9-fold at 72 h, P < 0.05) levels. In contrast, LV melusin mRNA levels remained unchanged in response to both infusions, as well as to aortic banding-induced pressure overload. Direct LV wall stress or late-stage hypertensive heart disease did not modify LV melusin gene expression either. Interestingly, in atrial HL-1 cells, cyclic stretching increased melusin mRNA levels. Stretching and treatments with hypertrophic agonists increased melusin mRNA and protein levels in NRVMs, endothelin-1 being the most potent. PD98059, an extracellular signal-regulated protein kinase 1/2 inhibitor, markedly attenuated the endothelin-1-induced upregulation of melusin gene expression in NRVMs.
  
  
  CONCLUSIONS
  Multiple hypertrophic stimuli regulate melusin expression predominately in the atria, which may represent a necessary initial step in early adaptive remodelling processes.
authors.affiliation: Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, Oulu, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Aro
authors.forename: H
authors.initials: H
authors.lastname: Tokola
authors.forename: V-P
authors.initials: VP
authors.lastname: Ronkainen
authors.forename: E
authors.initials: E
authors.lastname: Koivisto
authors.forename: O
authors.initials: O
authors.lastname: Tenhunen
authors.forename: M
authors.initials: M
authors.lastname: Ilves
authors.forename: I
authors.initials: I
authors.lastname: Szokodi
authors.forename: H
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: J
authors.initials: J
authors.lastname: Rysä
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006325:Heart Atria / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000235:genetics; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D012083:Renin / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors
chemical_list: C534931:AGT protein, human; D003598:Cytoskeletal Proteins; C582471:Itgb1bp2; C122158:Itgb1bp2 protein, mouse; D009124:Muscle Proteins; D012333:RNA, Messenger; D000808:Angiotensinogen; D001127:Arginine Vasopressin; D012083:Renin