Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: A gender-specific phenotype

Xiao Jun Du, Chrishan S. Samuel, Xiao Ming Gao, Ling Zhao, Laura J. Parry, Geoffrey W. Tregear

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136 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)395-404
Number of pages10
JournalCardiovascular Research
Volume57
Issue number2
DOIs
Publication statusPublished - 1 Feb 2003
Externally publishedYes

Keywords

  • Fibrosis
  • Gender
  • Gene expression
  • Hormones
  • Ventricular function

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