Effects of fish oil on inflammation and vascular function in claudicants

描述（由申请人提供）：估计有800 - 1200万美国人患有外周动脉疾病（PAD），导致显著的发病率和死亡率。尽管目前可用的药物和手术治疗，PAD患者发生心血管事件和死亡的风险仍然高得令人无法接受。因此，改善发病率和死亡率的干预措施至关重要。新兴研究表明，炎症、血管功能和PAD预后之间存在相互关系。生活方式的改变，包括运动和饮食，可能会潜在地改善症状，并调节影响这些患者疾病进展和长期预后的因素。长期以来，人们一直认为鱼油对心血管健康有益，尽管最近存在争议。最近的研究已经出现了n-3多不饱和脂肪酸（PUFA）存在于鱼油在终止炎症的作用。这一角色为食用鱼油的益处提供了新的视角。此外，我们的研究小组最近证明，omega-3指数（红细胞中n-3 PUFA含量的测量指标）与PAD患者的炎症呈负相关，其他研究表明，补充n-3 PUFA可以改善血管功能。因此，总体证据表明，鱼油可能在PAD的炎症过程和血管功能障碍的调节中发挥关键作用。我的长期目标是增加我们对营养和生活方式改变如何减轻PAD疾病负担的理解。因此，我本研究的目的是确定高剂量n-3 PUFA口服补充剂是否会改善PAD患者的全身炎症、血管功能和行走能力。这将通过一项双盲、随机、安慰剂对照试验进行评估，70名年龄在50岁至50岁之间的PAD患者接受4.4 g/天的n-3 PUFA，持续3个月。具体的测量将包括炎症和炎症终止的标记，血管功能的测量和行走测试。本文提出的研究有可能为营养干预在PAD中的作用提供重要的新见解，并提高我们对补充鱼油对心血管疾病的影响的理解。它将支持国家心脏、肺和血液研究所减少全球心脏、肺和血液疾病负担的目标。这里介绍的培训计划和研究方案旨在提高我作为一名独立临床试验人员的技能，并由在临床试验、外科、生物统计学、血管生物学和分子生物学方面具有广泛专业知识的多学科导师团队提供支持。这项研究将在旧金山退伍军人事务医疗中心（SFVAMC）进行，这是美国资金最充足、科学知识最丰富的退伍军人事务中心之一。此外，我将获得SFVAMC和UCSF的机构支持和资源。培训计划、指导和科学环境将为我提供成功完成这个项目所需的资源，并使我走上成为独立研究者和领域领导者的道路。

DESCRIPTION (provided by applicant): An estimated 8-12 million Americans suffer from peripheral artery disease (PAD), leading to significant morbidity and mortality. Despite current available medical and surgical therapies, patients with PAD continue to be at an unacceptably high risk for cardiovascular events and death. Accordingly, interventions to improve morbidity and mortality are critical. Emerging research demonstrates the inter-related effects of inflammation, vascular function and outcomes in PAD. Lifestyle modifications, including exercise and diet, may potentially improve symptoms, as well as modulate factors that influence disease progression and long-term outcomes in these patients. Fish oil has long been recognized to have beneficial effects on cardiovascular health, despite recent controversy. Recent studies have emerged on the role of n-3 polyunsaturated fatty acids (PUFA) present in fish oil in the termination of inflammation. This role offers new perspectives on the benefits of fish oil consumption. Furthermore, our group recently demonstrated that the omega-3 index, a measure of n-3 PUFA content in red blood cells, is inversely related to inflammation in patients with PAD, and others have shown that n-3 PUFA supplementation can improve vascular function. Hence, overall evidence suggests that fish oil could play a key role in the regulation of inflammatory processes and vascular dysfunction that characterize PAD. My long-term goal is to increase our understanding of how nutritional and lifestyle modifications can reduce the burden of disease in PAD. Accordingly, my goal with the present study is to determine if high-dose n-3 PUFA oral supplementation will improve systemic inflammation, vascular function, and the walking ability of patients with PAD. This will be evaluated using a double-blind, randomized, placebo-controlled trial of 70 patients aged e 50 with PAD receiving 4.4 g/day of n-3 PUFA for 3 months. Specific measurements will include markers of both inflammation and termination of inflammation, measures of vascular function, and a walking test. The study proposed here has the potential to provide important new insights on the role of nutritional interventions in PAD, as well as to improve our understanding of the effects of fish oil supplementation in cardiovascular diseases. It will support the goal of the National Heart, Lung and Blood Institute of reducing the burden of heart, lung, and blood diseases worldwide. The training plan and study protocol presented here are designed to advance my skills as an independent clinical trialist, supported by a multidisciplinary team of mentors with broad expertise in clinical trials, surgery, biostatistics, vascular biology, and molecular biology. The research will take place at the San Francisco Veterans Affairs Medical Center (SFVAMC), one of the most funded and scientifically knowledgeable VA centers in the United States. Furthermore, I will have access to institutional support and resources from both the SFVAMC and UCSF. The training plan, mentorship, and scientific environment will provide me with the resources necessary for the successful completion of this project, and place me on the path to become an independent investigator and leader in my field.