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Anti-Remodeling Effects of Xanthohumol-Fortified Beer in Pulmonary Arterial Hypertension Mediated by ERK and AKT Inhibition

Silva, Ana Filipa, Faria-Costa, Gabriel, Sousa-Nunes, Fábio, Santos, Manuel Filipe, Ferreira-Pinto, Manuel João, Duarte, Delfim, Rodrigues, Ilda, Tiago Guimarães, João, Leite-Moreira, Adelino, Moreira-Gonçalves, Daniel, Henriques-Coelho, Tiago, Negrão, Rita
Nutrients 2019 v.11 no.3
antineoplastic activity, apoptosis, beers, cell viability, ethanol, exercise test, hemodynamics, hypertension, laboratory animals, males, mitogen-activated protein kinase, monocrotaline, pathophysiology, phenotype, polyphenols, proteins, pulmonary artery, rats, vascular endothelial growth factor receptor-2
Polyphenols present in some alcoholic beverages have been linked to beneficial effects in preventing cardiovascular diseases. Polyphenols found in beer with anti-proliferative and anti-cancer properties are appealing in the context of the quasi-malignant phenotype of pulmonary arterial hypertension (PAH). Our purpose was to evaluate if the chronic ingestion of a xanthohumol-fortified beer (FB) would be able to modulate the pathophysiology of experimental PAH. Male Wistar rats with monocrotaline (MCT)-induced PAH (60 mg/kg) were allowed to drink either xanthohumol-fortified beer (MCT + FB) or 5.2% ethanol (MCT + SHAM) for a period 4 weeks. At the end of the protocol, cardiopulmonary exercise testing and hemodynamic recordings were performed, followed by sample collection for further analysis. FB intake resulted in a significant attenuation of the pulmonary vascular remodeling in MCT + FB animals. This improvement was paralleled with the downregulation in expression of proteins responsible for proliferation (ERK1/2), cell viability (AKT), and apoptosis (BCL-XL). Moreover, MCT + FB animals presented improved right ventricle (RV) function and remodeling accompanied by VEGFR-2 pathway downregulation. The present study demonstrates that a regular consumption of xanthohumol through FB modulates major remodeling pathways activated in experimental PAH.