Effects of Tart Cherry and Aroniaberry Supplementation on Endothelial Function and Cardiovascular Measures in Healthy Older Adults: Interactions with Genotype and Proteome

心血管疾病（CVD）仍然是全球死亡和残疾的主要原因。心血管疾病的发病和进展可能与年龄有关。衰老过程导致血管保护机制失效，导致病理生理变化和CVD风险增加。 心脏健康策略，包括富含水果和蔬菜的饮食，可以降低风险并预防心血管疾病。越来越多的实验证据表明，某些水果和浆果（包括樱桃和刺果）可能具有心脏保护作用，因为它们具有抗氧化和血管扩张作用，并且有益于调节免疫功能和炎症。然而，有有限的人类研究已经检查了这些影响。在老年人中，血管老化主要包括动脉僵硬度增加和内皮功能障碍。 氧化应激和炎症也与衰老过程有关。因此，本研究将研究酸樱桃和aroniaberry补充对内皮功能（流量介导的肱动脉扩张）和动脉僵硬度（心踝血管指数）的影响，作为心血管风险和动脉粥样硬化的指标。 这些测量还提供动脉结构和功能的评估。还将检查内皮功能障碍、炎症、血管损伤、氧化、脂质、一氧化氮状态以及类黄酮和酚酸特征的生物标志物。重要的是，遗传学及其环境相互作用作为CVD的因果因素的作用尚未完全了解。关于血浆蛋白质组和饮食或营养素干预可能导致的生理过程变化的数据也很有限。本研究将探讨对酸樱桃或aroniaberry补充剂的反应与研究结果和CVD风险相关基因座中的单核苷酸多态性（SNP）之间的关联。此外，还将研究这两种补充剂与参与几种生理途径和CVD的血浆蛋白质的蛋白质组学面板之间的关联。在一项随机、双盲、安慰剂对照、交叉临床试验中，96名健康的老年人（55-70岁）将在日常饮食中每天交替服用酸樱桃和aroniaberry补充剂，每次持续3周。本研究将包括6次访视，间隔3周，包括治疗期、洗脱期和安慰剂期。 这项研究将提供重要的信息黄酮丰富的营养素的作用和它们对动脉结构和功能的影响。 将基因组和蛋白质组特征与本研究的结果相关联将有助于开发未来的治疗策略以降低CVD风险。

Cardiovascular disease (CVD) continues to be the leading cause of death and disability worldwide. Cardiovascular disease can be age-related in both onset and progression. The aging process causes failure in protective vascular mechanisms leading to pathophysiological changes and increased risk of CVD. Heart healthy strategies including consumption of diets rich in fruits and vegetables reduce risk and prevent CVD. There is growing experimental evidence that certain fruits and berries including, cherries and aroniaberries, may be cardioprotective due to their antioxidant and vasodilatory properties, and beneficial modulation of immune function and inflammation. However, there are limited human studies that have examined these effects. In older adults, vascular aging predominantly includes increased arterial stiffness and endothelial dysfunction. Oxidative stress and inflammation are also linked to the aging process. Therefore, this study will investigate the effects of tart cherry and aroniaberry supplementation on endothelial function (flow-mediated brachial artery dilation) and arterial stiffness (cardio-ankle vascular index) as indicators of cardiovascular risk and atherosclerosis. These measurements also provide an assessment of arterial structure and function. Biomarkers of endothelial dysfunction, inflammation, vascular injury, oxidation, lipids, nitric oxide status, as well as flavonoid and phenolic acid profiles will also be examined. Importantly, the role of genetics and its environmental interactions as causal factors in CVD is not completely understood. There is also limited data on the plasma proteome and the changes in physiological processes that may result from interventions with diet or nutrients. This study will explore the association between responses to tart cherry or aroniaberry supplementation and single nucleotide polymorphisms (SNPs) in loci related to the study outcomes and to the risk of CVD. Moreover, the association between these two supplements and a proteomic panel of plasma proteins involved in several physiological pathways and CVD will also be investigated. In a randomized, double-blind, placebo-controlled, crossover clinical trial, 96 healthy older adults (ages 55-70) will be given tart cherry alternating with aroniaberry supplementation daily for 3 weeks each while on their usual diet. This study will include 6 visits at 3 week intervals consisting of treatment, washout and placebo periods. This investigation will provide important information on the role of flavonoid-rich nutrients and their effect on arterial structure and function. Relating genomic and proteomic signatures to the outcomes of this study will be useful in developing future therapeutic strategies to lower CVD risk.