Advanced glycation end products and cardiovascular disease

晚期糖基化终末产物与心血管疾病

• 批准号: 7726388
• 负责人: RICHARD D SEMBA
• 金额: $ 41万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7726388
• 关键词: Address; Adult; Advanced Glycosylation End Products; Age; Aging; Atherosclerosis; Binding; Biological; Blood; Blood Vessels; Body Composition; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Cell membrane; Cell surface; Cleaved cell; Clinical Distribution; Collagen; Communities; Coronary heart disease; Country; Data; Diabetes Mellitus; Diet; Diet Modification; Dietary intake; Disabled Persons; Elderly; Enrollment; Food; General Population; Health; Heart failure; High temperature of physical object; Human; Inflammation; Inflammatory; Insulin Resistance; Interleukin-6; Intervention; Knowledge; Life; Ligands; Low Density Lipoprotein oxidation; Measures; Morbidity - disease rate; Myocardial Infarction; Outcome; Pathogenesis; Pathway interactions; Peripheral arterial disease; Pharmacological Treatment; Physiologic pulse; Plasma; Play; Process; Prospective Studies; Protein Isoforms; Proteins; Public Health; RNA Splicing; Receptor Activation; Risk; Risk Factors; Role; Serum; Source; Stroke; Tissues; Variant; Woman; arterial stiffness; base; cardiovascular risk factor; crosslink; diabetic; fasting plasma glucose; follow-up; glucose metabolism; glycation; improved; inflammatory marker; inhibitor/antagonist; insight; men; modifiable risk; mortality; novel; older men; oral glucose tolerance; prevent; public health relevance; receptor; receptor binding; receptor for advanced glycation endproducts

DESCRIPTION (provided by applicant): Cardiovascular disease is the leading cause of morbidity and mortality in western countries. Advanced glycation end products (AGEs) are bioactive molecules implicated in the pathogenesis of atherosclerosis and cardiovascular disease. Major sources of systemic AGEs are endogenous AGEs generated in the body and exogenous AGEs found in foods. The western diet is rich in AGEs that are formed when food is processed at high temperatures. AGEs play a role in atherosclerosis by cross-linking collagen in vessel walls, increasing oxidation of low-density lipoprotein, and increasing inflammation through activation of the receptor for AGE (RAGE). Circulating isoforms of RAGE include endogenous secretory RAGE (esRAGE), a splice variant of RAGE that is secreted into blood and lacks the transmembrane and cytoplasmic portion of the receptor, and truncated forms of RAGE that have been cleaved from the cell surface. Based upon knowledge of the AGE-RAGE pathway and our preliminary data, we hypothesize that older people with elevated serum AGEs, sRAGE, and esRAGE are at greater risk of developing adverse cardiovascular outcomes, such as coronary heart disease, heart failure, stroke, and cardiovascular disease mortality. We propose to characterize the relationship between AGEs and circulating RAGE with cardiovascular outcomes in the NIH-supported Health, Aging and Body Composition (Health ABC) Study, a community-based prospective study of aging. Serum AGEs and circulating RAGE will be measured at enrollment and examined in relation to prevalent cardiovascular disease and to incident cardiovascular diseases that have been assessed over ten years of follow-up. Serum AGEs and circulating RAGE will also be examined in relation to aortic pulse wave velocity, abnormal glucose metabolism, and markers of inflammation. The proposed study will determine whether or not serum AGEs are a major risk factor for cardiovascular disease and will provide insight into the biological mechanisms by which serum AGEs and their circulating receptors may be involved in the pathogenesis of cardiovascular disease. AGEs are a potentially modifiable risk factor, as circulating AGEs can be lowered by dietary modification and by pharmacological intervention with AGE inhibitors or AGE-breakers. PUBLIC HEALTH RELEVANCE: This project is relevant to public health as it aims to characterize the relationship between advanced glycation end products, bioactive compounds found in high amounts in the western diet, and cardiovascular disease in older adults.

描述（由申请人提供）：心血管疾病是西方国家发病和死亡率的主要原因。晚期糖基化最终产物（年龄）是与动脉粥样硬化和心血管疾病的发病机理有关的生物活性分子。系统年龄的主要来源是体内产生的内源性年龄，是食品中发现的外源性年龄。西方饮食在高温下处理食物时形成的年龄丰富。年龄通过血管壁中的交联胶原蛋白在动脉粥样硬化中发挥作用，增加了低密度脂蛋白的氧化，并通过激活受体的年龄（RAGE）来增加炎症。愤怒的循环同工型包括内源性分泌愤怒（ESRAGE），这是一种愤怒的剪接变异，被分泌到血液中，缺乏受体的跨膜和细胞质部分，以及截断的愤怒形式，这些愤怒形式已被裂开。基于对年龄段途径和我们的初步数据的了解，我们假设血清年龄升高，SRAGE和ESRAGE的老年人更容易发生心血管疾病，例如冠心病，心脏衰竭，中风和心血管疾病死亡率。我们建议在NIH支持的健康，衰老和身体组成（健康ABC）研究中表征年龄与循环愤怒之间的关系，这是一项基于社区的前瞻性衰老研究。血清年龄和循环愤怒将在入学时测量，并在患有患心血管疾病的患病和心血管疾病中进行检查。血清年龄和循环愤怒也将与主动脉脉冲波速度，异常葡萄糖代谢和炎症标志有关。拟议的研究将确定血清年龄是否是心血管疾病的主要危险因素，并将洞悉血清年龄及其循环受体可能参与心血管疾病发病机理的生物学机制。年龄是一个潜在的可修改风险因素，因为循环年龄可以通过饮食修改以及与年龄抑制剂或破坏年龄的药理学干预来降低循环年龄。公共卫生相关性：该项目与公共卫生有关，旨在表征先进的糖基化最终产品，西方饮食中大量的生物活性化合物以及老年人的心血管疾病之间的关系。