Heart failure (HF) affects approximately 5.1 million people in the United States (US), and diagnoses have remained consistent with more than 650,000 new cases every year [1]. The five-year survival rate after diagnosis is approximately 50%. While HF primarily affects the elderly, considering the growing age of the population, 1 in 33 individuals in the US will have HF by the year 2030, leading to a near doubling in healthcare costs [2]. HF is characterized by reduced ejection fraction (EF) and increased left ventricular (LV) wall thickening due to structural and functional defects of the heart (3). This can be initiated by ischemia in human HF by a myocardial infarct. This modified cardiac load increases stress of the ventricular wall, leading to structural remodeling due to cardiomyocyte hypertrophy and apoptosis as well as fibrosis [3].

Inflammation and oxidative stress play integral roles in the development of HF [4]. Hypoxia alone can induce inflammation and cell death [5], causing release of damage associated molecular patterns (DAMPs), which can bind to toll-like receptor (TLR)4 in neighboring cells [6], potentiating an inflammatory response. Reactive oxygen species (ROS) derived from NADPH-oxidases (NOX), xanthine oxidase (XO) and mitochondria are classically considered the primary sources of ROS [7], [8], [9] in the failing heart, while superoxide dismutase (SOD), NADPH quinone dehydrogenase (NQO1), catalase (CAT), and glutathione peroxidase (GPx) are responsible for antioxidant defense, and counteract ROS [10,11]Both inflammation and ROS can promote cardiomyocyte apoptosis, fibrosis and cardiac dysfunction [12,13]. TLR4 signaling activates inflammatory signaling pathways including mitogen-activated protein kinases (MAPKs): p38MAPK, extracellular signal‑regulated protein kinase (ERK1/2) and stress-activated protein kinases (SAPK)/Jun amino-terminal kinases (JNK) [14], [15], [16], [17]. This leads to phosphorylation and translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [18] into the cell nucleus, leading to the transcription of inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α [19,20]. Inflammation facilitates macrophage recruitment into the myocardium via chemoattractants and also leads to differentiation of fibroblasts intro myofibroblasts, promoting fibrosis [21]. Thus, these inflammatory and redox pathways play key regulatory roles in the pathogenesis of HF and their regulation is of clinical significance.

Raspberries are a rich source of polyphenols [22], and these polyphenols may target numerous molecular pathways involved in HF as our group has previously summarized [23]. Nonetheless, the ability of raspberries to modulate cardiac function, inflammation and oxidative stress in a model of HF has not been previously investigated. Thus, the objective of this study was to determine whether raspberry consumption could improve functional parameters and morphological characteristics of the heart in rats with HF and investigate the molecular pathways which may be involved in mediating these effects.