Lp(a) and Oxidized Phospholipids - Impact of Diets

Lp(a) 和氧化磷脂 - 饮食的影响

• 批准号: 10367048
• 负责人: Enkhmaa Byambaa
• 金额: $ 61.46万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367048
• 关键词: Address; Adopted; Adult; Affect; African American population; Alpha Particles; Apolipoproteins A; Biological; Black Populations; Carbohydrates; Cardiovascular Diseases; Characteristics; Cholesterol; Clinical; Complex; Data; Diet; Dietary Intervention; Environment; Funding; Genes; Genetic; Genetic Polymorphism; Goals; Heart; Heterogeneity; Individual; Insulin Resistance; Intake; Intervention Studies; Knowledge; LDL Cholesterol Lipoproteins; Laboratories; Life Style Modification; Lipoprotein (a); Lipoproteins; Maps; Measures; Mediating; Meta-Analysis; Metabolic; Metabolic syndrome; Modeling; Nonpharmacologic Therapy; Oxides; Pattern; Phospholipids; Plasma; Population; Prevention; Property; Race; Randomized; Regimen; Research; Risk; Saturated Fatty Acids; Subgroup; Testing; United States National Institutes of Health; Unsaturated Fats; apolipoprotein Lp(a+); base; cardiovascular disorder risk; cardiovascular disorder therapy; cardiovascular risk factor; dietary; dietary guidelines; evidence based guidelines; feeding; healthy lifestyle; improved; lipidomics; non-genetic; precision nutrition; racial and ethnic; response; thrombogenesis

PROJECT SUMMARY/ABSTRACT An elevated level of plasma lipoprotein(a) [Lp(a)] is an independent causal risk factor for cardiovascular disease (CVD). Lifestyle modifications, including dietary changes, are recommended as first line therapy to reduce CVD risk. Dietary guidelines to lower saturated fatty acids (SFA) and replace them with unsaturated fats or complex carbohydrates target primarily low-density lipoprotein cholesterol (LDL-C). In the small number of dietary studies that assessed Lp(a) level, a consistent increase was found in response to reduction in SFA intake. As LPA gene controls Lp(a) level and very few non-genetic factors impact Lp(a), this diet-mediated effect is notable. Importantly, the increase in Lp(a) level is a counter observation to the effect of SFA reduction on LDL-C. The mechanism(s) underlying this paradoxical finding and furthermore how SFA reduction affects Lp(a) atherogenic properties beyond its plasma level remains unknown. Lp(a) carries the majority of circulating proinflammatory and proatherogenic oxidized phospholipids (OxPL) and Lp(a) atherogenicity is mediated by its OxPL content. Despite this, little is known about what happens to OxPL when dietary SFA is reduced and its major lipoprotein carrier is increased. This proposal will bridge these knowledge gaps and obtain a more complete picture of CVD risk manipulation through SFA reduction consistent with current dietary guidelines. The central hypothesis—Lp(a)-OxPL content is increased with dietary SFA replacement diminishing the beneficial effect of LDL-C lowering on CVD risk—will be tested through a comprehensive research in the largest and most diverse platform consisting of three NIH-funded well-controlled metabolic feeding trials (DELTA 1, DELTA 2, and GET-READI). Specifically, the dynamics of changes in Lp(a)-OxPL in response to SFA reduction will be assessed using quantitative (total concentration) (Aim 1) and qualitative (subspecies composition) (Aim 3) approaches in both healthy and metabolically challenged individuals. Replacement strategies for SFA reduction (unsaturated fats vs. complex carbohydrate) and genetic variability modelled via the apolipoprotein(a) size polymorphism will be tested as response modulators. Specific subgroups (e.g., ethnic/racial, those with and without metabolic burden) who may benefit the least (or the most) from the generalized dietary guidelines to reduce SFA intake will be identified (Aim 2). As clinical laboratory values for LDL-C include Lp(a) cholesterol, the opposing effect of SFA reduction on these two lipoproteins, therefore, likely results in an inaccurate estimation of the true LDL-C response. This critical issue will be mapped in more detail. The findings originating in the largest and most diverse compilation of data will improve the understanding of a common non-pharmacological therapy that may enhance the atherogenic potential of Lp(a) beyond its plasma level. Ultimately, this will assist in adopting precision nutrition as part of a heart-healthy lifestyle for an improved CVD risk prevention and management.

项目摘要/摘要 血浆脂蛋白水平升高（a）[LP（a）]是心血管的独立因果风险因素 疾病（CVD）。建议对生活方式的改变，包括饮食变化，作为第一线治疗 降低CVD风险。降低饱和脂肪酸（SFA）的饮食指南，并用不饱和的 脂肪或复杂的碳氢化物靶向原代低密度脂蛋白胆固醇（LDL-C）。在少数 在评估LP（a）水平的饮食研究中，发现SFA的减少而发现了一致的增加 进气。由于LPA基因控制LP（a）水平，而非遗传因素很少影响LP（a），该饮食介导的 效果是值得注意的。重要的是，LP（a）水平的增加是对SFA降低效果的反见 在LDL-C上。这种自相矛盾的发现的基础机制，以及SFA还原如何影响 LP（A）超出其血浆水平的动脉粥样硬化特性尚不清楚。 LP（a）携带大部分循环 促炎和促进性氧化的磷脂（OXPL）和LP（A）动脉粥样硬化是由其介导的 OXPL含量。尽管如此，对于减少饮食SFA而对OXPL的情况知之甚少 主要的脂蛋白载体增加。该建议将弥合这些知识差距，并获得更多 通过减少SFA的降低与当前的饮食指南一致的CVD风险操纵的完整图片。 中心假设-lp（a）-Oxpl含量随着饮食SFA的替代而增加 LDL-C降低对CVD风险的有益作用 - 将通过一项全面研究来测试 最大，最潜水员的平台由三个由NIH资助的良好控制的代谢喂养试验组成 （Delta 1，Delta 2和Get-Readi）。具体而言，响应于Lp（a）-oxpl的变化的动力学响应于 SFA减少将使用定量（AIM 1）和定性（亚种）进行评估 组成）（目标3）在健康和代谢挑战的个体中采用的方法。替代品 SFA还原的策略（不饱和脂肪与复杂碳水化合物）和通过建模的遗传变异性 载脂蛋白（A）大小多态性将作为响应调节剂进行测试。特定的子组（例如， 种族/种族，有和没有代谢伯恩的人）可能会从中受益最少（或最多） 将确定减少SFA摄入量的广义饮食指南（AIM 2）。作为临床实验室值 LDL-C包括LP（A）胆固醇，SFA降低对这两种脂蛋白的相反作用，因此 可能导致对真实LDL-C反应的估计不准确。这个关键问题将被映射到更多 细节。起源于最大和最潜水员的数据的发现将改善 了解可能增强LP的动脉粥样硬化潜力的常见非药物疗法（a） 超出了血浆水平。最终，这将有助于采用精确营养作为心脏健康的一部分 改善CVD风险预防和管理的生活方式。