Endogenous Anti-Inflammatory Lipid Mediators, Fish Oil and Post-Operative Atrial

内源性抗炎脂质介质、鱼油和术后心房

• 批准号: 8399046
• 负责人: DARIUSH MOZAFFARIAN
• 金额: $ 23.06万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8399046
• 关键词: 11-dehydro-thromboxane B2; Acute; Affect; Ancillary Study; Animal Disease Models; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Atrial Fibrillation; Biological Markers; C-reactive protein; Cardiac Surgery procedures; Cardiovascular system; Chronic Disease; Clinical; Complication; Development; Diet; Dietary Fatty Acid; Double-Blind Method; Enrollment; Epoxy Compounds; Fatty Acids; Fish Oils; Funding; Future; Health; Heart; Heart Atrium; Human; In Vitro; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Injury; Intake; Interleukin-6; Investigation; Lead; Left; Leukotriene E4; Link; Measurement; Measures; Metabolism; Modeling; Mono-S; Omega-3 Fatty Acids; Operative Surgical Procedures; Oral; Outcome; Pathway interactions; Patients; Placebos; Plasma; Polyunsaturated Fatty Acids; Population; Postoperative Period; Prevention; Randomized; Randomized Controlled Trials; Research; Research Infrastructure; Resources; Risk; Risk Factors; Role; Supplementation; Testing; Therapeutic; Time; Tissues; Urine; Work; clinically relevant; cost; cost effective; double-blind placebo controlled trial; improved; innovation; insight; lipid mediator; novel; response; response to injury; sample collection; urinary

DESCRIPTION (provided by applicant): Although inflammation has been linked to development of several chronic diseases, including of the cardiovascular system, emerging evidence suggests that recently identified endogenous anti-inflammatory molecules may be critical for appropriate control and protection against injury and excessive inflammation. In vitro and animal studies suggest that Mono-Epoxides derived from long-chain polyunsaturated Fatty Acids (MEFAs) are crucial for reducing inflammatory responses to injury, including in the heart. While there is promising evidence in animal disease models, the metabolism and anti-inflammatory function of MEFAs in humans remain largely unexplored. This proposed work will evaluate for the first time the relationships of plasma MEFAs with circulating and urine pro-inflammatory mediators in a human model of acute injury/inflammation, i.e. cardiac surgery. This work represents a highly innovative use of a human model of discrete and well-timed tissue injury to elucidate the biologic roles and relevance of MEFAs in humans. This is made possible by nesting our proposed study in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation (OPERA) Trial, a randomized, double-blind, placebo controlled trial among 1516 cardiac surgery patients to test the effects of peri-operative oral fish oil on both biologic endpoints, including pro- inflammatory biomarkers, and clinical endpoints including post-operative atrial fibrillation (POAF). The study has existing funding for subject enrollment, sample collection/storage, and ascertainment/measurement of these endpoints. Although MEFAs are metabolites of fish-oil-derived fatty acids, the impact of dietary fish oil on MEFAs response to acute injury/inflammation in humans is unknown. By nesting this biologic research within OPERA, an existing randomized controlled trial of fish oil, we will be able to directly evaluate the unbiased effects of oral fish oil intake on MEFAs response to injury/inflammation. These results will have tremendous significance for understanding how dietary fatty acids affect MEFAs response, and represent a second highly innovative aspect of this work. Finally, given the focus of OPERA on POAF, we will be able to evaluate at no additional cost the potential relevance of MEFAs response to this clinically relevant outcome, a common and serious complication of cardiac surgery. We will perform this novel work by measuring plasma levels of MEFAs and their metabolites in a randomly selected subset of patients (n=800) in OPERA, and then assessing the interrelationships of MEFAs level with biomarkers of inflammation; the effects of oral fish oil treatment, vs. placebo, on these MEFAs response; and the relationship of MEFAs levels with POAF.

描述（由申请人提供）：尽管炎症已与包括心血管系统在内的多种慢性疾病的发展有关，但新兴证据表明，最近发现的内源性抗炎分子可能对适当控制和保护损伤和过度炎症至关重要。体外和动物研究表明，源自长链多不饱和脂肪酸（MEFAS）的单环毒素对于减少包括心脏在内的损伤的炎症反应至关重要。尽管在动物病模型中有有希望的证据，但MEFA在人类中的代谢和抗炎功能在很大程度上仍未得到探索。这项拟议的工作将首次评估血浆MEFA与急性损伤/炎症模型（即心脏手术）模型中循环和尿液促炎性介体的关系。这项工作代表了人类的离散组织损伤模型的高度创新使用，以阐明MEFA在人类中的生物学作用和相关性。通过将我们提出的研究嵌套在Omega-3脂肪酸中，以预防术后心房颤动（Opera）试验（Opera）试验，这是一项随机，双盲，安慰剂对照试验，对1516名心脏手术患者中的一项试验，以测试围场术术的术语术语术语和临床上的临床生物终点，并包括术语术的效果，以及临床上的临床上的生物标准，并纤颤（POAF）。这项研究拥有现有的资金，用于入学，样本收集/存储以及这些终点的确定/测量。尽管MEFA是鱼油衍生的脂肪酸的代谢产物，但饮食鱼油对人类急性损伤/炎症反应的影响尚不清楚。通过将这项生物学研究嵌套在《鱼油的现有随机对照试验》（Opera）中，我们将能够直接评估口腔鱼油摄入对MEFAS对损伤/炎症的反应的无偏影响。这些结果对于理解饮食脂肪酸如何影响MEFA的反应将具有巨大的意义，并代表了这项工作的第二个高度创新的方面。最后，鉴于歌剧的重点放在POAF上，我们将不得评估MEFAS对这种临床相关结果的潜在反应的潜在相关性，这是心脏手术的常见和严重的并发症。我们将通过在歌剧中随机选择的患者子集中测量MEFA的血浆水平及其代谢物来进行这项新工作，然后评估MEFAS水平与炎症生物标志物的相互关系；口服鱼油处理的影响，与安慰剂，对这些MEFA的反应；以及MEFAS水平与POAF的关系。

项目成果

Fish oil vs olive oil for postoperative atrial fibrillation--reply.

鱼油与橄榄油治疗术后心房颤动 - 回复。

• DOI: 10.1001/jama.2013.673
• 发表时间: 2013
• 期刊: JAMA
• 作者: Mozaffarian,Dariush;Marchioli,Roberto
• 通讯作者: Marchioli,Roberto

Circulating and dietary omega-3 and omega-6 polyunsaturated fatty acids and incidence of CVD in the Multi-Ethnic Study of Atherosclerosis.

• DOI: 10.1161/jaha.113.000506
• 发表时间: 2013-12-18
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: de Oliveira Otto MC;Wu JH;Baylin A;Vaidya D;Rich SS;Tsai MY;Jacobs DR Jr;Mozaffarian D
• 通讯作者: Mozaffarian D

Biomarkers of dairy fatty acids and risk of cardiovascular disease in the Multi-ethnic Study of Atherosclerosis.

• DOI: 10.1161/jaha.113.000092
• 发表时间: 2013-07-18
• 期刊: Journal of the American Heart Association
• 影响因子: 5.4
• 作者: de Oliveira Otto MC;Nettleton JA;Lemaitre RN;Steffen LM;Kromhout D;Rich SS;Tsai MY;Jacobs DR;Mozaffarian D
• 通讯作者: Mozaffarian D