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

1 Lady Davis Institute for Medical Research and 2 Department of Pathology, Sir Mortimer B. Davis-Jewish General Hospital, Montreal H3T 1E2; and 3 Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, Quebec, Canada H3A 1A3 Unmanipulated early growth response-1 (Egr-1)-deficient / mice have similar heart-to-body weight ratios but express lower amounts of atrial natriuretic factor (ANF), -myosin heavy chain ( -MHC), skeletal actin, NGF1-A binding protein (NAB)-2, Sp1, c- fos , c- jun , GATA-4, and Nkx2.5 than +/+ or +/ mice. -MHC, tubulin, and NAB-1 expression was similar. Isoproterenol (Iso) and phenylephrine (PE) infusion into +/+ and / mice increased heart weight, ANF, -MHC, skeletal actin, Sp1, NAB-2, c- fos , and c- jun expression, 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 / mice displayed fibrosis and increased Sp1, skeletal actin, Nkx2.5, and GATA-4 expression without hypertrophy. Minipump removal caused the agonist-treated hearts and gene expression to regress to control or near-control levels. Thus Egr-1 deficiency caused a blunted catecholamine-induced hypertrophy response and increased sensitivity to stress. catecholamines; gene expression