Etanercept attenuates short-term cigarette-smoke-exposure-induced pulmonary arterial remodelling in rats by suppressing the activation of TNF-α/NF-κB signal and the activities of MMP-2 and MMP-9

The pathogenesis of cigarette-smoke-exposure-induced pulmonary vasculature impairment is unclear. Cigarette-smoke-exposure-induced the accumulation of tumour necrosis factor-alpha (TNF-alpha) and up-regulates the expression and activities of matrix metalloproteinases (MMPs) involved in smoke-induced vascular remodelling, which are important processes in the pathogenesis of vasculature impairment. The TNF-alpha antagonist Etanercept is an anti-inflammatory drug with a potential role in regulating MMP expression. To determine the effect of Etanercept on short-term smoke-induced pulmonary arteriole impairment and investigate its possible mechanism, male Sprague Dawley rats were exposed to cigarette-smoke daily for two weeks in both the absence and presence of Etanercept. Cigarette-smoke-exposure-induced elevation of mean pulmonary artery pressures and medial hypertrophy of pulmonary arterioles were partially reduced by Etanercept. Up-regulation of the expression and activities of MMP-2 and MMP-9, induced by cigarette-smoke, were also suppressed significantly by Etanercept. Furthermore, Etanercept treatment significantly attenuated cigarette-smoke-induced TNF-alpha accumulation and activation of nuclear factor NF-kappa B signal. These results suggest that Etanercept have the protective effects in cigarette-smoke-induced pulmonary vascular remodelling, with the attenuation of the up-regulated expression and activities of MMP-2 and MMP-9 and activation of TNF-alpha/NF-kappa B signal pathway probably being involved as part of its mechanism. Our study might provide insight into the development of new interventions for vasculature impairment. (C) 2012 Elsevier Ltd. All rights reserved.