Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype.
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.
Du
Xiao-Jun
XJ
Experimental Cardiology Laboratory, Baker Medical Research Institute, PO Box 6492, St Kilda Road Central, Melbourne, Vic. 8008, Australia. xiaojun.du@baker.edu.au
Samuel
Chrishan S
CS
Gao
Xiao-Ming
XM
Zhao
Ling
L
Parry
Laura J
LJ
Tregear
Geoffrey W
GW
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
D012065:Relaxin; D003094:Collagen