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）仍然是世界范围内死亡和残疾的主要原因。心血管疾病的发病和进展都与年龄有关。衰老过程导致血管保护机制失效，导致病理生理变化，增加心血管疾病的风险。包括食用富含水果和蔬菜的饮食在内的心脏健康策略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，包括樱桃和黑莓，可能具有保护心脏的作用，因为它们具有抗氧化和血管扩张的特性，对免疫功能和炎症有有益的调节作用。然而，对这些影响进行检验的人体研究有限。在老年人中，血管老化主要包括动脉僵硬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，本研究将探讨酸樱桃和野樱莓补充剂对内皮功能（血流介导的肱动脉扩张）和动脉硬度（心踝血管指数）作为心血管风险和动脉粥样硬化指标的影响。这些测量还提供了动脉结构和功能的评估。内皮功能障碍、炎症、血管损伤、氧化、脂质以及类黄酮和酚酸谱的生物标志物也将被检查。重要的是，遗传及其环境相互作用作为心血管疾病的致病因素的作用尚不完全清楚。关于血浆蛋白质组和饮食或营养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樱莓补充剂的反应与研究结果和心血管疾病风险相关位点的单核苷酸多态性（snp）之间的关系。此外，还将研究这两种补充剂与参与几种生理途径和心血管疾病的血浆蛋白质组学面板之间的关系。在一项随机、双盲、安慰剂对照、交叉临床试验中，96名健康老年人（55-70岁）在正常饮食的同时，每天交替服用酸樱桃和野莓补充剂，持续3周。这项研究将包括6次访问，每3周一次，包括治疗期、洗脱期和安慰剂期。本研究将为揭示富含类黄酮的营养素的作用及其对动脉结构和功能的影响提供重要信息。将基因组和蛋白质组学特征与这项研究的结果联系起来，将有助于制定未来降低心血管疾病风险的治疗策略。

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,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.