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The Role of Egr-1 in the Cardiac Remodeling During Chronic Pressure Overload


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 Early growth response-1 (Egr-1) is a transcription factor which is activated in the left ventricle during the onset of myocardial hypertrophy in response to pressure overload, but its role in cardiac remodeling is still unclear. The recent generation by homologous recombination of mice which have ablated Egr-1 allows to explore this issue. In particular, we exposed Egr-1 null mice (-/-, n=18) and their wild-type littermates (+/+, n=20) to chronic pressure overload induced by transverse aortic constriction (TAC) between left carotid artery and truncus anonimus. In sham operated mice (+/+ n=6; -/- n=7) basal fractional shortening, as an index of left ventricular function evaluated by transthoracic echocardiography, (47.4±.6 vs 48.4±.7 %, n.s.) and left ventricular weight/body weight ratio (LVW/BW, mg/g), an index of left ventricular mass, (3.2±.1 vs 3.1±.1 mg/g, n.s.) were comparable in +/+ and -/- mice. After 7 days of chronic pressure overload, despite systolic pressure gradient across the stenosis was comparable between the two mice strains (62±5 vs 67±6 mmHg, n.s.), -/- mice showed a lower LVW/BW as compared to +/+ mice (4.4±.2 vs 5.7±.3 mg/g, p<0.01). Moreover, the histological analysis disclosed a markedly reduced left ventricle perivascular and interstitial fibrosis in -/- TAC mice as compared to that observed in +/+ TAC mice. Interestingly, left ventricular gene expression of fibronectin and collagen I and III was significantly reduced in -/- TAC mice when compared with +/+ TAC mice. These data demonstrate that Egr-1 activation affects the stromal reaction involved in the cardiac remodeling due to pressure overload, suggesting that Egr-1 may be a molecular target of novel therapeutic strategies focused to modulate specific features of the cardiac hypertrophic remodeling.