Altered molecular response to adrenoreceptor-induced cardiac hypertrophy in Egr-1-deficient mice

Unmanipulated early growth response-1 (Egr-1)-deficient -/- mice have simil ar heart-to-body weight ratios but express lower amounts of atrial natriure tic factor (ANF), beta-myosin heavy chain (beta-MHC), skeletal actin, NGF1- A binding protein (NAB)-2, Sp1, c-fos, c-jun, GATA-4, and Nkx2.5 than +/+ o r +/- mice. alpha-MHC, tubulin, and NAB-1 expression was similar. Isoproter enol (Iso) and phenylephrine (PE) infusion into +/+ and -/- mice increased heart weight, ANF, P-MHC, skeletal actin, Spl, NAB-2, c-fos, and c-jun expr ession, but induction in -/- mice was lower. Only Iso + PE-treated +/+ mice showed induction of NAB-1, GATA-4, and Nkx2.5. Foci of fibrosis were found in Iso + PE-treated -/- and +/+ mice. Surprisingly, vehicle-treated -/- mi ce displayed fibrosis and increased Sp1, skeletal actin, Nkx2.5, and GATA-4 expression without hypertrophy. Minipump removal caused the agonist-treate d hearts and gene expression to regress to control or near-control levels. Thus Egr-1 deficiency caused a blunted catecholamine-induced hypertrophy re sponse and increased sensitivity to stress.