Raspberry polyphenols attenuate heart failure by modulating underlying molecular drivers of disease

Introduction: Individuals with heart failure (HF) have a 50% five-year mortality even with modern pharmacological approaches. Thus, alternative therapeutic options are urgently needed. Raspberries are a rich source of polyphenols which have a wide range of bioactive properties and can target cellular pathways involved in HF at the molecular level. Thus, the objective of this study was to investigate the therapeutic potential of raspberry consumption in a model of HF. Hypothesis: We hypothesized that the consumption of raspberries could attenuate the development of HF in rats. Methods: Six-week-old male Sprague Dawley rats consumed either a control diet or a 10% raspberry supplemented diet for three weeks. Rats then underwent a sham operation (control diet only) or permanent ligation of the left anterior descending coronary artery to induce HF (control diet and 10% raspberry diet). Rats continued their diets following surgery for four additional weeks. Echocardiograms were then conducted followed by sacrifice. Hearts were excised for left ventricle protein analysis via Western Blot. Data were analyzed by one-way ANOVA followed by Tukey-Kramer post-hoc analysis. Significance refers to a P-value <0.05. Results: Ejection fraction significantly declined in control diet animals with HF compared to sham (39 ± 6% vs 70 ± 5%); however, the 10% raspberry diet significantly attenuated this reduction (51 ± 3%). There was also a significant increase in left ventricle (LV) mass in control diet animals with HF compared to sham (1,066 ± 140 mg vs 1,670 ± 683 mg), while there were no significant differences in LV mass in the 10% raspberry diet (1,405 ± 285 mg). The nuclear localization of nuclear factor kappa B (NF-κB) was significantly increased in left ventricles of HF animals compared to both sham and the 10% raspberry diet group. The expression of the pro-remodeling cytokine, transforming growth factor (TGF)-β, as well as matrix metalloproteinases (MMP)2 and 9 were significantly increased in HF animals consuming a control diet compared to both sham animals and the 10% raspberry diet group. Phosphorylated ERK1/2, a regulator of cardiac hypertrophic signaling, was expressed in a similar manner. Summary: These data indicate that the consumption of raspberries can reduce the underlying molecular drivers of HF, thus leading to the observed improvements in cardiac functional capacity and morphology. In conclusion, raspberry polyphenols attenuate HF by reducing inflammatory signaling, thus, mitigating proteins involved in cardiac remodeling and hypertrophy. Further investigation in humans is needed to confirm these findings. Agriculture and Food Research Initiative (Grant No. 2019-67017-29257) from USDA-NIFA and a USDA-NIFA predoctoral fellowship (Grant No. 2021-67034-35131). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.