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

Nutrients. 2019 Mar 9;11(3):583. doi: 10.3390/nu11030583.

Abstract

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.

Keywords: beer; monocrotaline; polyphenol; pulmonary arterial hypertension; remodeling; xanthohumol.

MeSH terms

  • Animals
  • Beer / analysis*
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Flavonoids / administration & dosage*
  • Flavonoids / chemistry
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hypertension, Pulmonary / chemically induced*
  • Hypertension, Pulmonary / pathology
  • Male
  • Monocrotaline / toxicity
  • Propiophenones / administration & dosage*
  • Propiophenones / chemistry
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Wistar
  • Vascular Remodeling / drug effects*

Substances

  • Flavonoids
  • Propiophenones
  • Monocrotaline
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • xanthohumol