Anti-remodeling effects of xanthohumol-fortified beer in pulmonary arterial hypertension mediated by ERK and AKT inhibition

• Main Author: Silva, AF
• Publication Date: 2019
• Other Authors: Faria-Costa, G, Sousa-Nunes, F, Santos, MF, Ferreira-Pinto, MJ, Duarte, D, Rodrigues, I, Guimarães, JT, Leite-Moreira, A, Moreira-Gonçalves, D, Henriques-Coelho, T, Negrão, R
• Format: Article
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: https://hdl.handle.net/10216/136302
• topic: Beer; Monocrotaline; Polyphenol; Pulmonary arterial hypertension; Remodeling; Xanthohumol

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.