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患者仍然处于不可接受的心血管事件和死亡的高风险中。因此，降低发病率和死亡率的干预措施至关重要。新兴的研究表明炎症、血管功能和PAD结局的相互影响。生活方式的改变，包括运动和饮食，可能会改善症状，并调节影响这些患者疾病进展和长期结局的因素。长期以来，鱼油一直被认为对心血管健康有有益的影响，尽管最近有争议。最近的研究表明，鱼油中存在的n-3多不饱和脂肪酸（PUFA）在终止炎症中的作用。这一作用为鱼油消费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）与PAD患者的炎症呈负相关，其他研究表明，n-3 PUFA补充剂可以改善血管功能。因此，总体证据表明，鱼油可能在调节PAD特征性炎症过程和血管功能障碍方面发挥关键作用。我的长期目标是增加我们对营养和生活方式改变如何减少PAD疾病负担的理解。因此，我本研究的目标是确定高剂量n-3 PUFA口服补充剂是否会改善全身炎症、血管功能和PAD患者的行走能力。这将使用一项双盲、随机、安慰剂对照试验进行评估，该试验纳入70名年龄在50岁以上的PAD患者，这些患者接受4. 4 g/天n-3 PUFA治疗3个月。具体的测量将包括炎症和炎症终止的标志物、血管功能的测量和行走试验。 这项研究有可能为营养干预在PAD中的作用提供重要的新见解，并提高我们对鱼油补充剂对心血管疾病影响的理解。它将支持国家心脏，肺和血液研究所的目标，即减少全球心脏，肺和血液疾病的负担。这里介绍的培训计划和研究方案旨在提高我作为独立临床试验者的技能，并得到多学科导师团队的支持，他们在临床试验，手术，生物统计学，血管生物学和分子生物学方面具有广泛的专业知识。这项研究将在旧金山弗朗西斯科退伍军人事务医疗中心（SFVAMC）进行，该中心是美国资金最多、科学知识最丰富的退伍军人事务中心之一。此外，我将有机会获得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该项目所需的资源，并使我成为我所在领域的独立调查员和领导者。

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.