Raspberry polyphenols target molecular pathways of heart failure

Abstract

Approximately 650,000 new cases of heart failure (HF) are diagnosed annually with a 50% five-year mortality rate. HF is characterized by reduced left ventricular (LV) ejection fraction and hypertrophy of the LV wall. The pathophysiological remodeling of the heart is mediated by increased oxidative stress and inflammation. Raspberries are rich in polyphenols which may favorably impact enzymes involved in redox homeostasis while also targeting inflammatory signaling. Thus, the objective of this study was to investigate whether raspberry polyphenols could attenuate HF. Sprague Dawley rats consumed a 10% (w/w) raspberry diet for 7 weeks. At week 3, HF was surgically induced via coronary artery ligation. Hemodynamics and morphology of the heart were assessed. Expression of cardiac proteins involved in oxidative stress, inflammation, apoptosis, and remodeling were examined, and histological analysis was conducted. Additionally, human cardiomyocytes were treated with raspberry polyphenol extract (RBPE) followed by CoCl2 to chemically induce hypoxia. Redox status, apoptosis, and mitochondrial dysfunction were measured. Raspberries attenuated reductions in cardiac function and reduced morphological changes which coincided with reduced toll-like receptor (TLR)4 signaling. Reductions in oxidative stress, apoptosis, and remodeling occurred in vivo. Incubation of cardiomyocytes with RBPE attenuated CoCl2-induced oxidative stress and apoptosis despite pronounced hypoxia-inducible factor (HIF)-1α expression. These data indicate that consumption of raspberries can reduce the underlying molecular drivers of HF; thus, leading to the observed improvements in cardiac functional capacity and morphology. This dietary strategy may be an effective alternative strategy for treating HF. However, further investigation into alternative models of HF is warranted.