Triptolide protects rat heart against pressure overload-induced cardiac fibrosis

Background: Emerging evidence underlines the role of inflammation activation in the process of cardiac fibrosis. Triptolide has potent anti-inflammatory and anti-proliferative properties, and extensively used in the treatment of chronic inflammatory disorders. In the current study, we test the hypothesis that triptolide treatment facilitates to attenuate chronic pressure overload-induced cardiac fibrosis in a model of rat. Methods: Adult male Sprague-Dawley rats were subjected to a suprarenal abdominal aorta constriction (AC) or sham (as control) to induce sustained pressure overload. Eight weeks later, rats were randomly assigned to receive triptolide (9 mu g/kg. d, i.p) or vehicle (0.1% dimethyl sulfoxide, 0.2 ml/d, i.p) treatment for an additional 8 weeks. Results: AC caused significant pathological hypertrophy, cardiac fibrosis and reduced cardiac diastolic function. Triptolide treatment markedly inhibited AC-induced increases in myocardial collagen volume fraction, collagen type I/III deposition, left ventricular end-diastolic pressure, expressions of pro-fibrogenic factors (transforming growth factor-beta and angiotensin II) and pro-inflammatory cytokines (IL-1 beta and IL-6), NF-kappa B activation and inflammatory cell infiltration in left ventricles compared with vehicle, without affecting cardiac hypertrophy. However, triptolide had no effects on systemic blood pressure and circulating angiotensin II level. Conclusions: Collectively, the findings suggested that triptolide treatment elicits favorable anti-fibrogenic effect in a blood pressure-independent manner, at least in part, through inhibiting myocardial pro-fibrogenic factor production and inflammatory activation in the pressure overloaded heart. (C) 2013 Elsevier Ireland Ltd. All rights reserved.