title: Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype.
abstract: OBJECTIVE
  To investigate cardiac phenotypes in mice deficient in the peptide hormone relaxin by gene targeting.
  
  
  METHODS
  Echocardiography and cardiac catheterization were performed on male and female relaxin deficient (Rlx(-/-)) mice as well as heterozygous (Rlx(+/-)) and wildtype (Rlx(+/+)) littermates aged between 8 and 24 months. Collagen expression and content in the heart were analysed by real-time PCR, hydroxyproline assay and histology.
  
  
  RESULTS
  Heart rate, blood pressures, left ventricular (LV) dimensions, fractional shortening and maximal and minimal dP/dt did not differ significantly between the three genotypes of either gender at any age. However, 8-10-month-old Rlx(-/-) males exhibited a greater transmitral flow velocity (A-wave) at the late LV diastolic phase. Male Rlx(-/-) mice aged between 12 and 24 months had significantly higher LV end-diastolic pressures, a 30% increase in atrial weight and 10-30% increases in lung and liver weights. Male mice also showed an age-dependent increase (P<0.01) in LV collagen content that was more pronounced in Rlx(-/-) than control littermates (P<0.01). Procollagen type-1 expression was also significantly higher in the LV of Rlx(-/-) males compared with either Rlx(+/-) or Rlx(+/+) males at 6, 9 and 12 months of age. Age-matched female Rlx(-/-) mice did not display any of these cardiac phenotypes seen in Rlx(-/-) males.
  
  
  CONCLUSIONS
  Male Rlx(-/-) mice had impeded LV diastolic filling and increased atrial weights, most likely due to an increase in ventricular collagen content and chamber stiffness. These phenotypes in the Rlx(-/-) males were not observed in Rlx(-/-) females, indicating the importance of other gender-related factors in cardiovascular function.
authors.affiliation: Experimental Cardiology Laboratory, Baker Medical Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Vic. 8008, Australia. xiaojun.du@baker.edu.au
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Du
authors.forename: Chrishan S
authors.initials: CS
authors.lastname: Samuel
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Parry
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Tregear
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006325:Heart Atria / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D010641:Phenotype; D012065:Relaxin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012727:Sex Characteristics; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D012065:Relaxin; D003094:Collagen