Mediterranean Dietary Intervention in Pediatric Hyperlipidemia

地中海饮食干预小儿高脂血症

• 批准号: 9148052
• 负责人: Marguerite Engler
• 金额: $ 20.29万
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9148052
• 关键词: 3' Untranslated Regions; Adult; Affect; Anti-Inflammatory Agents; Anti-inflammatory; Area; Arteries; Atherosclerosis; Behavior Therapy; Binding; Biological Availability; Biological Markers; Biological Process; Blood Vessels; Breast Cancer Cell; Cardiovascular Diseases; Cardiovascular system; Child; Childhood; Cholesterol; Cocoa Powder; Coronary heart disease; Development; Diet; Dietary Factors; Dietary Intervention; Dietary Supplementation; Disease; Endothelial Cells; Event; Fatty Acids; Gene Expression; Gene Targeting; Genetic; Goals; Growth; Health; Hyperlipidemia; In Vitro; Inflammation; Length; Lipids; Liver; Mediterranean Diet; Messenger RNA; MicroRNAs; Modification; Neoplasm Metastasis; Nitric Oxide; Nucleotides; Omega-3 Fatty Acids; Patients; Plague; Plasma; Platelet aggregation; Play; Prevention; Proanthocyanidins; Production; Regulator Genes; Risk; Role; Science; Site; Smooth Muscle; Therapeutic; Translating; Triglycerides; Untranslated RNA; Vasodilator Agents; early onset; endothelial dysfunction; extracellular; grape seed extract; high risk; improved; in vivo; insight; lipid disorder; oxidation; polyphenol; tumor

Atherosclerosis is a global concern and is a leading cause of cardiovascular events.1 Studies have shown that childhood cholesterol levels predict adult cholesterol levels, suggesting that children with high cholesterol levels are at high risk for atherosclerosis and early onset of coronary heart disease (CHD). Endothelial dysfunction, an important early event in the development of CHD,is present in children with high cholesterol levels before the formation of plagues within the arteries. The primary management of high cholesterol is lifestyle modification such as diet. Studies have shown that the Mediterranean diet is effective for the prevention of CHD. The cardioprotective effect of the Mediterranean diet may be attributed to the anti-oxidative and anti-inflammatory activities of the polyphenols abundant in the Mediterranean diet. Polyphenols are also known to improve vascular function by increasing the bioavailability of nitric oxide (NO), a potent endothelial-derived vasodilator. Several lines of evidence indicate that omega-3 fatty acid supplements also enhance endothelial function by stimulating release of NO from the endothelial cells, decreasing triglyceride concentration, and inhibiting platelet aggregation. MicroRNAs (miRNAs) are short noncoding RNA molecules that have approximately 22 nucleotides in length. They regulate gene expression by binding to complementary sites on the 3 untranslated regions of target mRNAs, which causes the mRNA to be degraded and translated less. As negative regulators of gene expression, miRNAs are crucially involved in a variety of biological processes in health and diseases including cardiovascular disease. Surprisingly, miRNAs are detected in serum and plasma, and they are known to be remarkably stable. Recent studies have revealed that these extracellular microRNAs are differently expressed in healthy people and those with hyperlipidemia or CHD. For example, miRNA -122 and miRNA-370 are significantly increased in hyperlipidemia patients compared with controls. According to in-vivo and in-vitro studies, miRNA-122 and miR-370 play important roles in fatty acid synthesis and oxidation. Another study has shown that circulating levels of vascular miRNAs (miRNA 126, miRNA17, miRNA92a), inflammation-associated miRNA (miRNA 155), and smooth muscle-enriched miRNA (miRNA 145) are significantly lower in patient with CHD compared with healthy controls. Studies that have investigated the impact of dietary supplementation on miRNA expression are very limited. Nevertheless, a few in-vitro studies have demonstrated that omega-3 fatty acids significantly inhibit expression of miRNA-21 which is known to contribute to the growth and metastasis of tumors originating from breast cancer cells. Interstingly, proanthocyanidin extracted from grape seed and cocoa upregulated miR-197,25 of which a target gene plays a central role in liver lipid production. Despite the great potential of dietary interventions on modification of miRNA expression, little is known how the diet changes miRNA expression. Understanding the effect of dietary factors on miRNA expression and function may provide insight into therapeutic strategies to reduce the burden of hyperlipidemia in children.

动脉粥样硬化是全球关注的问题，是心血管事件的主要原因。1研究表明，儿童胆固醇水平可以预测成人胆固醇水平，这表明胆固醇水平高的儿童患动脉粥样硬化和早期冠心病心脏病（CHD）的高风险。 内皮功能障碍是CHD发展的重要早期事件，在动脉内瘟疫之前具有高胆固醇水平的儿童。 高胆固醇的主要管理是生活方式的修改，例如饮食。 研究表明，地中海饮食对预防CHD有效。 地中海饮食的心脏保护作用可能归因于地中海饮食中多酚的抗氧化和抗炎活性。 还已知多酚通过增加一氧化氮（NO）的生物利用度（一种有效的内皮衍生的血管扩张剂）来改善血管功能。 几条证据表明，Omega-3脂肪酸补充剂还通过刺激从内皮细胞中释放NO，降低甘油三酸酯的浓度并抑制血小板聚集来增强内皮功能。 microRNA（miRNA）是短的非编码RNA分子，长度约为22个核苷酸。它们通过与靶标mRNA的3个未翻译区域上的互补位点结合来调节基因表达，从而导致mRNA降解和翻译较少。作为基因表达的负调节剂，miRNA在健康和疾病中的多种生物学过程中至关重要，包括心血管疾病。 令人惊讶的是，在血清和血浆中检测到miRNA，众所周知它们非常稳定。最近的研究表明，这些细胞外的microRNA在健康的人和高脂血症或冠心病患者中的表达不同。 例如，与对照组相比，高脂血症患者的miRNA -122和miRNA -370显着增加。 根据体内和体外研究，miRNA-122和miR-370在脂肪酸合成和氧化中起重要作用。 另一项研究表明，与健康对照组相比，患者的血管miRNA水平（miRNA 126，miRNA17，miRNA92A），与炎症相关的miRNA（miRNA 155）和平滑肌富含miRNA（miRNA 145）显着降低。 研究了补充饮食对miRNA表达的影响的研究非常有限。然而，一些体外研究表明，omega-3脂肪酸显着抑制miRNA-21的表达，而miRNA-21的表达有助于源自乳腺癌细胞的肿瘤的生长和转移。 杂文中，从葡萄种子和可可提取的原蛋白素上调了miR-197,25，其中靶基因在肝脂质产生中起着核心作用。 尽管饮食干预措施对miRNA表达的改变具有很大的潜力，但鲜为人知的饮食如何改变miRNA表达。 了解饮食因素对miRNA表达和功能的影响可能会洞悉治疗策略，以减轻儿童高脂血症的负担。