Abstract
We have previously shown that mice with homozygous deletion of the pro-atrial natriuretic peptide (ANP, Nppa−/−) gene exhibit left ventricular (LV) hypertrophy at baseline and exaggerated hypertrophy after pressure overload induced by transverse aortic constriction (TAC). Nppa−/− mice have increased expression of extracellular matrix molecules, i.e. metalloproteinase-2 and tissue inhibitor of metalloproteinase-3 and cardiac remodeling after TAC.
A single copy of the pro-ANP gene (Nppa+/−) will not be adequate to protect heterozygous mice against exaggerated LV hypertrophy resulting from pressure overload stress. Therefore, Nppa+/− mice will have exaggerated cardiac remodeling compared to wild type Nppa+/+ mice after pressure overload stress. Cardiac remodeling in Nppa+/− mice will be less marked than in Nppa−/− animals.
Nppa+/−, Nppa−/− and Nppa+/+ mice were subjected to TAC. Mice were fed a normal NaCl diet. One week after TAC, echocardiography was performed, hearts were removed and weighted.
The heterozygote is a novel model for studying LV hypertrophy and the transition to failure during pressure overload stress. It is less abnormal than Nppa−/− at baseline and may more closely resemble the human condition.
Am J Hypertens (2004) 17, 86A–87A; doi: 10.1016/j.amjhyper.2004.03.222
