TY - JOUR
T1 - A genetic locus accentuates the effect of volume overload on adverse left ventricular remodeling in male and female rats
AU - Souzeau, Emmanuelle
AU - Llamas, Bastien
AU - Bélanger, Sonia
AU - Picard, Sylvie
AU - Deschepper, Christian F.
PY - 2006/1
Y1 - 2006/1
N2 - Although increased left ventricular (LV) mass is highly predictive of cardiovascular morbidity and mortality in humans, it has never been verified in an experimental model that naturally occurring alleles linked to increased LV mass under basal conditions also associate with worsened cardiovascular prognosis. Because we have shown previously that locus Cm24 on chromosome 5 was responsible for differences in LV mass between WKY and WKHA rats, we used WKY.WKHA-(D5Rat45-D5Rat245) congenic rats (where locus Cm24 has been transferred from WKHA into WKY rats) to test how naturally occurring gene variants present in Cm24 would, in addition to their effects under basal conditions, affect LV mass remodeling and/or function in the context of overload. Volume overload was induced in WKY, WKHA, and WKY.WKHA congenic rats by surgical creation of an aorto-caval fistula. In females, the fistula had no effect on the hearts of WKY rats, yet it induced dilated eccentric hypertrophy and isolated diastolic dysfunction in WKHA and WKY.WKHA congenic rats, along with signs of congestive heart failure. In males, the surgical maneuver induced only mild or inconsistent responses in WKY rats but had much more pronounced effects in WKHA and WKY.WKHA congenic rats. Altogether, our data show that a genetic locus that induces, under basal conditions, either mild or no concentric LV remodeling in either male or female rats, respectively, associates with LV dilatation and dysfunction in both sexes when the hearts are additionally challenged.
AB - Although increased left ventricular (LV) mass is highly predictive of cardiovascular morbidity and mortality in humans, it has never been verified in an experimental model that naturally occurring alleles linked to increased LV mass under basal conditions also associate with worsened cardiovascular prognosis. Because we have shown previously that locus Cm24 on chromosome 5 was responsible for differences in LV mass between WKY and WKHA rats, we used WKY.WKHA-(D5Rat45-D5Rat245) congenic rats (where locus Cm24 has been transferred from WKHA into WKY rats) to test how naturally occurring gene variants present in Cm24 would, in addition to their effects under basal conditions, affect LV mass remodeling and/or function in the context of overload. Volume overload was induced in WKY, WKHA, and WKY.WKHA congenic rats by surgical creation of an aorto-caval fistula. In females, the fistula had no effect on the hearts of WKY rats, yet it induced dilated eccentric hypertrophy and isolated diastolic dysfunction in WKHA and WKY.WKHA congenic rats, along with signs of congestive heart failure. In males, the surgical maneuver induced only mild or inconsistent responses in WKY rats but had much more pronounced effects in WKHA and WKY.WKHA congenic rats. Altogether, our data show that a genetic locus that induces, under basal conditions, either mild or no concentric LV remodeling in either male or female rats, respectively, associates with LV dilatation and dysfunction in both sexes when the hearts are additionally challenged.
KW - Gender
KW - Genetics
KW - Heart failure
KW - Hypertrophy
KW - Myocardium
KW - Myocytes
KW - Natriuretic peptides
UR - http://www.scopus.com/inward/record.url?scp=31744445026&partnerID=8YFLogxK
U2 - 10.1161/01.HYP.0000196732.22719.47
DO - 10.1161/01.HYP.0000196732.22719.47
M3 - Article
C2 - 16344368
AN - SCOPUS:31744445026
SN - 0194-911X
VL - 47
SP - 128
EP - 133
JO - Hypertension
JF - Hypertension
IS - 1
ER -