FLAVANOL-RICH COCOA TO REVERSE VASCULAR DISEASE OF AGING

富含黄烷醇的可可可逆转衰老性血管疾病

• 批准号: 7032250
• 负责人: NAOMI D FISHER
• 金额: $ 8.54万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7032250
• 关键词: age difference; aging; alcoholic beverages; arginine; atherosclerosis; cardiovascular disorder; cardiovascular disorder chemotherapy; clinical research; enzyme inhibitors; flavonoids; human subject; medicinal plants; myocardial infarction; nitric oxide synthase; plant extracts; stroke; tea; vasodilation

DESCRIPTION (provided by applicant): Research Objective: Cardiovascular Aging Advancing age is accompanied by an increased prevalence of cardiovascular disease, including atherosclerosis, myocardial infarction, and stroke. Underlying all of these conditions lies the aging blood vessel, damaged with a dysfunctional endothelium. Evidence has secured aging as a strong predictor of endothelial dysfunction, yet potential therapies are unknown. Consumption of flavonoid-rich beverages, including tea and red wine, is associated with a reduction in coronary events. Cocoa can contain extraordinary concentrations of flavonoids, shown to activate nitric oxide synthase (NOS) in vitro. We have demonstrated that cocoa rich in these flavonoids induced peripheral vasodilation, improving endothelial function in healthy people. Furthermore, through infusion of the specific NOS inhibitor L-NAME, we have demonstrated that the mechanism is nitric-oxide dependent. We propose that responsiveness to these flavonoids, namely via activation of NOS, is age-dependent, increasing with advancing age. Specifically, we plan to extend preliminary observations that the beneficial effects of flavonoid-rich cocoa on augmenting endothelial function are greater in the elderly than in the young. Pulse wave amplitude will be measured in the finger in response to flavanol-rich cocoa, with flavanol-poor cocoa as a control. To test the hypothesis that these actions are dependent upon NO synthesis, we will measure responsiveness to the naturally occurring substrate L-arginine before and after one week of flavanol-rich cocoa in elderly subjects. We anticipate that the vasodilator effects of arginine will be enhanced after flavanol-rich cocoa, and that L-NAME will inhibit the response. With this proposal Dr. Fisher will enter a new area of clinical research in cardiovascular aging, with investigations into improvement of endothelial function that are novel, intriguing and broadly applicable. She will be solely responsible for planning, directing and executing the proposed two-year project on the GCRC of the Brigham and Women's Hospital. She will be well-positioned to submit an application for an RO1 with results from this study. Therapeutic interventions aimed at restoring vascular endothelial function hold tremendous clinical promise.

描述（由申请人提供）： 研究目的：心血管衰老随着年龄的增长，心血管疾病的患病率增加，包括动脉粥样硬化、心肌梗塞和中风。所有这些病症的根源在于老化的血管，以及因功能失调的内皮细胞而受损的血管。有证据表明衰老是内皮功能障碍的有力预测因素，但潜在的治疗方法尚不清楚。 饮用富含类黄酮的饮料，包括茶和红酒，与减少冠状动脉事件有关。可可含有极高浓度的类黄酮，在体外可激活一氧化氮合酶 (NOS)。我们已经证明，富含这些类黄酮的可可可诱导外周血管舒张，改善健康人的内皮功能。此外，通过输注特定的 NOS 抑制剂 L-NAME，我们已经证明该机制是一氧化氮依赖性的。我们认为，对这些类黄酮的反应，即通过一氧化氮合酶的激活，是年龄依赖性的，随着年龄的增长而增加。具体来说，我们计划扩展初步观察结果，即富含类黄酮的可可对增强内皮功能的有益作用在老年人中比年轻人更大。将测量手指中的脉搏波振幅，以响应富含黄烷醇的可可，并以缺乏黄烷醇的可可作为对照。为了检验这些作用依赖于一氧化氮合成的假设，我们将测量老年受试者在食用富含黄烷醇的可可前后一周对天然底物 L-精氨酸的反应。我们预计，在食用富含黄烷醇的可可后，精氨酸的血管舒张作用将会增强，而 L-NAME 会抑制这种反应。通过这项提议，费舍尔博士将进入心血管衰老临床研究的新领域，对内皮功能的改善进行新颖、有趣且广泛适用的研究。她将全权负责规划、指导和执行布莱根妇女医院 GCRC 拟议的为期两年的项目。她将能够根据本研究的结果提交 RO1 申请。旨在恢复血管内皮功能的治疗干预具有巨大的临床前景。