Resolvin E1 normalizes contractility, Ca2+ sensitivity and smooth muscle cell migration rate in TNF-α- and IL-6-pretreated human pulmonary arteries

American Journal of Physiology. Lung Cellular and Molecular Physiology
Roddy HiramEric Rousseau

Abstract

Pulmonary hypertension (PH) is a rare disease in which pathophysiology is characterized by an increase in proinflammatory mediators, chronic endothelial dysfunctions, and a high migration rate of smooth muscle cells (SMC). Over the course of the last decade, various treatments have been proposed to relax the pulmonary arteries, none of which have been effective in resolving PH. Our hypothesis is that artery-relaxing drugs are not the long-term solution, but rather the inhibition of tissue inflammation, which underlies human pulmonary artery (HPA) dysfunctions that lead to abnormal vasoconstriction. The goal of the present study was to assess the anti-inflammatory effects of resolvin E1 (RvE1) with concomitant effects on SMC migration and on HPA reactivity. The role and mode of action of RvE1 and its precursor, monoacylglyceride eicosapentaenoic acid were assessed on HPA under proinflammatory conditions, involving a combined pretreatment with 10 ng/ml TNF-α and 10 ng/ml IL-6. Our results show that TNF-α and IL-6 treatment induced hyperreactivity and Ca(2+) hypersensitivity in response to pharmaco-mechanical stimuli, including 80 mM KCl, 1 μM phorbol 12-13-dibutyrate, and 30 nM U-46619. Furthermore, the proinflammatory treatment ...Continue Reading

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Citations

May 3, 2018·Physiological Reviews·Nandini KrishnamoorthyBruce D Levy
Oct 16, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Y S Prakash
Nov 3, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·John C HuetschLarissa A Shimoda
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Dec 28, 2016·BioMed Research International·Claudia GonzálezManuel Villalón
Jul 10, 2019·Experimental and Therapeutic Medicine·Jin XieWenxing Fan
Aug 1, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Armond DaciGokce Topal

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