Mechanistic insights into the vascular effects of blueberries: Evidence from recent studies

Abstract

Cardiovascular disease is the leading cause of death in the United States. Dietary habits influence a variety of cardiovascular complications such as peripheral artery disease, heart failure, and kidney disease. We along with others have previously reported the cardiovascular beneficial effects of dietary flavonoids. Anthocyanins, one class of flavonoids widely available in berries, have recently drawn wide scientific attention because of their diverse health benefits. Epidemiological, clinical, and animal studies indicate that blueberry anthocyanins exert protection against cardiovascular complications by acting on multiple targets in the vascular system. These include activating endothelial nitric oxide synthase signaling, reducing oxidative stress, improving inflammatory pathways, and ameliorating dyslipidemia. Anthocyanins are extensively metabolized in humans suggesting that their vascular benefits are likely mediated by their circulating metabolites. However, the bioactivities of blueberry metabolites are unknown. Evaluating the bioactivities of metabolites, analyzing their structure-activity relationship, and well-designed human trials are needed to understand the potential vascular effects of blueberries and their metabolites. Understanding the vascular effects will provide a solid scientific foundation to recommend blueberries to improve vascular health. This review highlights the recent developments in the understanding of the vascular effects of blueberries with special emphasis on the molecular mechanisms involved.

Blueberry Metabolites Attenuate Lipotoxicity‐Induced Endothelial Dysfunction

“…In support of our hypothesis, palmitate‐induced monocyte binding to HAECs was prevented in HAECs treated with blueberry metabolites (Figure A). This is clinically relevant because exaggerated monocyte binding to the endothelium is a key initial event in the pathogenesis of endothelial dysfunction . In contrast, the parent anthocyanins failed to exert such a protective effect (Figure A).…”

“…Studies in cultured cells, isolated arteries, animal models, and humans demonstrate that lipotoxicity has strong potential to impair NO production. Endothelial cell derived NO has vasodilatory, anti‐inflammatory, and antiproliferative properties . As such, any mismatch between production and destruction of this molecule has potential to precipitate cardiovascular complications.…”

“…ROS play a major role in the development of endothelial dysfunction and NOX is an important source of ROS in the vasculature . Palmitate can increase NOX levels in ECs that are associated with ROS production .…”

“…Blueberries are an excellent source of anthocyanins that include galactosides, glucosides, and arabinosides of cyanidin, delphinidin, malvidin, peonidin, and petunidin . Recent studies showed that consumption of blueberries improves endothelial function in subjects with metabolic syndrome, reduces blood pressure in postmenopausal women with hypertension, and increases flow‐mediated dilation in healthy individuals . However, the mechanisms responsible for the vascular benefits of blueberry anthocyanins are unknown.…”

Bioavailable Blueberry‐Derived Phenolic Acids at Physiological Concentrations Enhance Nrf2‐Regulated Antioxidant Responses in Human Vascular Endothelial Cells

“…Epidemiological studies, together with animal and clinical research, suggest that blueberry fruit intake is associated with health benefits related to improved endothelial and vascular functions . Acute (<24 h) and chronic (6–8 weeks) intake of blueberries have been shown to benefit endothelial function, evaluated as improved brachial flow‐mediated dilation or peripheral arterial tone in healthy adults .…”