© 2002 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout mouse hearts under chronic aortic stenosis
aDepartment of Pharmacology and Cell Biophysics, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0575, USA
bDivision of Xenobiotics, Metabolism and Disposition, National Institute of Health Sciences, Setagaya, Tokyo 158-8501, Japan
cDepartment of Cardiovascular Biology, Millennium Pharmaceuticals Inc., Cambridge, MA 02139, USA
dDivision of Cardiology, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106-5029, USA
litsa.kranias{at}uc.edu
* Corresponding author. Tel.: +1-513-5582-377; fax: +1-513-5582-269
Objective: To determine whether the hyperdynamic phospholamban-knockout hearts are capable of withstanding a chronic aortic stenosis. Methods: The transverse section of the aorta was banded in phospholamban-knockout and their isogenic wild-type mice, which were followed with echocardiography in parallel, along with sham-operated mice, before and at 2.5, 5 and 10 weeks after surgery. Results: Cardiac decompensation was evidenced by the presence of lung congestion in some banded knockouts and wild-types, giving rise to a subset of non-failing and failing hearts within each group. The incidence of heart failure was not genotype-dependent but rather associated with higher heart rates before surgery. The development of left ventricular hypertrophy was similar between knockouts and wild-types and longitudinal assessment of end-diastolic dimension indicated progressive increases after banding, with a greater dilation in failing mice. Fractional shortening was reduced in failing knockouts and wild-types to a similar degree, with an earlier onset in the knockouts. In addition, fractional shortening was decreased in non-failing knockouts but not wild-types. Ejection times shortened after aortic banding particularly for failing hearts. Assessment of the SR Ca2+-ATPase protein levels indicated similar downregulation for failing knockouts and wild-types, while the phospholamban levels were not significantly altered in wild-types. Conclusion: The hyperdynamic phospholamban-knockout hearts are able to compensate against a sustained aortic stenosis similar to wild-types.
KEYWORDS Ca-pump; Heart failure; Hypertrophy; SR (function); Ventricular function
1 Current address: Zentrum Innere Medizin, Abteilung Kardiologie und Pneumologie, Georg-August-Universität Göttingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany.
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