Abstract 18105: Genetic Deletion of IL-6 Attenuates Pressure Overload-Induced Left Ventricular Hypertrophy and Failure

Increasing evidence indicates a role of proinflammatory cytokines in the pathogenesis of myocardial hypertrophy and failure. Chronic interleukin-6 (IL-6) stimulation leads to LV hypertrophy and dysfunction, and deletion of IL-6 reduces LV hypertrophy after angiotensin II infusion. In this study, we tested the hypothesis that genetic deletion of IL-6 would ameliorate pressure overload-induced myocardial hypertrophy and failure. We performed transverse aortic constriction (TAC) in IL-6 knockout (IL6 KO) mice and wild-type (WT) C57BL/6J mice (control) to induce pressure overload. Cardiac structure and function were assessed by serial echocardiography prior to and until 42 days after TAC. Pressure overload induced progressive LV hypertrophy, remodeling, and dysfunction in WT control mice compared with baseline (BSL) (Figure). At 6 wks after TAC, these adverse effects of pressure overload were significantly attenuated in IL6 KO mice, as evidenced by smaller LV mass and greater LV EF compared with controls (Figure). We conclude that genetic deletion of IL-6 attenuates LV remodeling and dysfunction induced by pressure overload. These data suggest a possible therapeutic potential of IL-6 inhibition to ameliorate LV hypertrophy and dysfunction in patients with systemic hypertension.