Hypertrophy and functional alterations in hyperdynamic phospholamban-knockout mouse hearts under chronic aortic stenosis.
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 Ca(2+)-ATPase protein levels indicated similar downregulation for failing knockouts and wild-types, while the phospholamban levels were not significantly altered in wild-types.


CONCLUSIONS
The hyperdynamic phospholamban-knockout hearts are able to compensate against a sustained aortic stenosis similar to wild-types.
Kiriazis
Helen
H
Department of Pharmacology and Cell Biophysics, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH 45267-0575, USA.
Sato
Yoji
Y
Kadambi
Vivek J
VJ
Schmidt
Albrecht G
AG
Gerst
Michael J
MJ
Hoit
Brian D
BD
Kranias
Evangelia G
EG
D000818:Animals; D001017:Aortic Coarctation / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics*; D000252:Calcium-Transporting ATPases / Q000032:analysis; D002155:Calsequestrin / Q000032:analysis; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D004452:Echocardiography; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D013997:Time Factors; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D002155:Calsequestrin; D000099211:Phospholamban