Role of Osteopontin in Angiotensin II-induced cardiac fibrosis and remodeling

Abstract

Objective: Osteopontin (OPN) is up-regulated in several experimental models of cardiac remodeling, but its direct effects remain unclear. We investigated the role of OPN in the development of cardiac fibrosis and remodeling using OPN-deficient mice. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, against cardiac fibrosis and remodeling, was mediated through the inhibition of OPN expression in wild-type mice. Methods: Wild-type and OPN-deficient mice were treated with angiotensin II (AII) for 4 weeks. Wild-type mice receiving AII were divided into two groups, a control group and an Ep treatment group. Results: AII treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in wild-type mice. Ep treatment and OPN-deficiency could reduce the AII-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas only Ep treatment abolished the development of cardiac hypertrophy. Conclusions: These results suggest that OPN has a pivotal role in the development of AII-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.