TY - JOUR
T1 - Biventricular adaptation to volume overload in mice with aortic regurgitation
AU - Berry, Christopher J.
AU - Miller, Jordan D.
AU - McGroary, Kellyann
AU - Thedens, Daniel R.
AU - Young, Stephen G.
AU - Heistad, Donald D.
AU - Weiss, Robert M.
N1 - Funding Information:
This work was funded by grant #'s RR017369 (RMW), P01HL062984(DDH), and K99HL092235(JDM) from the National Institutes of Health.
PY - 2009
Y1 - 2009
N2 - Background. Aortic valve regurgitation is usually caused by impaired coaptation of the aortic valve cusps during diastole. Hypercholesterolemia produces aortic valve lipid deposition, fibrosis, and calcification in both mice and humans, which could impair coaptation of cusps. However, a link between hypercholesterolemia and aortic regurgitation has not been established in either species. The purpose of this study was to ascertain the prevalence of aortic regurgitation in hypercholesterolemic mice and to determine its impact on the left and right ventricles. Methods and Results. Eighty Ldlr-/-/ Apob100/100/Mttpfl/fl/Mx1Cre+/+ ("Reversa") hypercholesterolemic mice and 40 control mice were screened for aortic regurgitation (AR) with magnetic resonance imaging at age 7.5 months. The prevalence of AR was 40% in Reversa mice, with moderate or severe regurgitation (AR+) in 19% of mice. In control mice, AR prevalence was 13% (p = 0.004 vs. Reversa), and was invariably trace or mild in severity. In-depth evaluation of cardiac response to volume overload was performed in 12 AR-positive and 12 AR-negative Reversa mice. Regurgitant fraction was 0.34 0.04 in AR-positive vs. 0.02 0.01 in AR-negative (mean SE; p < 0.001). AR-positive mice had significantly increased left ventricular end-diastolic volume and mass and reduced ejection fraction in both ventricles. When left ventricular ejection fraction fell below 0.60 in AR-positive (n = 7) mice, remodeling occurred and right ventricular systolic function progressively worsened. Conclusion. Hypercholesterolemia causes aortic valve regurgitation with moderate prevalence in mice. When present, aortic valve regurgitation causes volume overload and pathological remodeling of both ventricles.
AB - Background. Aortic valve regurgitation is usually caused by impaired coaptation of the aortic valve cusps during diastole. Hypercholesterolemia produces aortic valve lipid deposition, fibrosis, and calcification in both mice and humans, which could impair coaptation of cusps. However, a link between hypercholesterolemia and aortic regurgitation has not been established in either species. The purpose of this study was to ascertain the prevalence of aortic regurgitation in hypercholesterolemic mice and to determine its impact on the left and right ventricles. Methods and Results. Eighty Ldlr-/-/ Apob100/100/Mttpfl/fl/Mx1Cre+/+ ("Reversa") hypercholesterolemic mice and 40 control mice were screened for aortic regurgitation (AR) with magnetic resonance imaging at age 7.5 months. The prevalence of AR was 40% in Reversa mice, with moderate or severe regurgitation (AR+) in 19% of mice. In control mice, AR prevalence was 13% (p = 0.004 vs. Reversa), and was invariably trace or mild in severity. In-depth evaluation of cardiac response to volume overload was performed in 12 AR-positive and 12 AR-negative Reversa mice. Regurgitant fraction was 0.34 0.04 in AR-positive vs. 0.02 0.01 in AR-negative (mean SE; p < 0.001). AR-positive mice had significantly increased left ventricular end-diastolic volume and mass and reduced ejection fraction in both ventricles. When left ventricular ejection fraction fell below 0.60 in AR-positive (n = 7) mice, remodeling occurred and right ventricular systolic function progressively worsened. Conclusion. Hypercholesterolemia causes aortic valve regurgitation with moderate prevalence in mice. When present, aortic valve regurgitation causes volume overload and pathological remodeling of both ventricles.
UR - http://www.scopus.com/inward/record.url?scp=70349562539&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349562539&partnerID=8YFLogxK
U2 - 10.1186/1532-429X-11-27
DO - 10.1186/1532-429X-11-27
M3 - Article
C2 - 19671155
AN - SCOPUS:70349562539
SN - 1097-6647
VL - 11
JO - Journal of Cardiovascular Magnetic Resonance
JF - Journal of Cardiovascular Magnetic Resonance
IS - 1
M1 - 27
ER -