INTIMAL THICKENING & ANTITOXIDANTS IN HISPANICS & ANGLOS

内膜增厚

• 批准号: 6530663
• 负责人: JAMES H DWYER
• 金额: $ 80.09万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530663
• 关键词: Hispanic Americans; antioxidants; artery occlusion; ascorbate; atherosclerosis; biomarker; cardiovascular disorder epidemiology; carotenoids; carotid artery; caucasian American; clinical research; dietary constituent; disease /disorder proneness /risk; gender difference; human subject; longitudinal human study; low density lipoprotein; nutrition related tag; racial /ethnic difference; vascular endothelium; vascular resistance

DESCRIPTION: (Adapted from Investigator's Abstract) Cardiovascular diseases remain the major causes of disability and early death in the U.S., and improved treatment and prevention will stem from knowledge of the etiology of atherosclerosis (Ath). The Los Angeles Atherosclerosis Study (LAAS) is a longitudinal investigation of the etiology of Ath focusing on diet and oxidative mechanisms in a randomly selected cohort of 573 utility workers, with oversampling of Hispanics. Preliminary results include a protective relation between plasma oxygenated carotenoids and 1.3 year change in the intima-media thickness (IMT) of the common carotid arteries, causal interpretation of which is supported by the findings that lutein inhibits monocyte attraction by LDL oxidized in a model of the artery wall, and that lutein supplementation reduced atherosclerosis extent by 86 percent in apo E null mice. Also, higher intake of vitamin C from supplements was significantly associated with increased progression of carotid IMT. In contrast, higher intake of vitamin C from food was associated with reduced progression of carotid IMT, but this protective relation was not significant. The protective relation of HDL-C with IMT was enhanced by higher plasma, beta-cryptoxanthin and by increased plasma level of an enzyme (paraoxonase, PON) that destroys oxidized lipids. This application proposes continued observation of the LAAS cohort with the addition of two ultrasound measures of arterial dysfunction and the investigation of new etiologic factors for Ath suggested by laboratory findings of collaborators. Additional observations will also increase power for detecting relations with IMT. The new risk factors focus on pathways that promote or inhibit LDL damage and inflammatory responses in the artery wall. The new measures of arterial function and dysfunction are (1) endothelial function of the brachial artery (lumen diameter increase in response to hyperemia); and (2) distensibility or stiffness of the common carotid artery. These additional measures, together with those in the original protocol, will allow investigation of relations between longitudinal change in Ath and dietary antioxidants, antioxidant enzymes, and genetic polymorphisms.

描述：（改编自研究者摘要）心血管疾病 仍然是美国残疾和早逝的主要原因，和改进 治疗和预防将源于对病原学的了解， 动脉粥样硬化（Ath）。洛杉矶动脉粥样硬化研究（LAAS）是一项 Ath病因的纵向调查，重点是饮食和 在随机选择的573名公用事业工人的队列中， 西班牙裔的过度抽样初步结果包括保护关系 血浆含氧类胡萝卜素与内膜中层1.3年变化之间的关系 颈总动脉内膜中层厚度（IMT），其因果关系解释 叶黄素抑制低密度脂蛋白对单核细胞的吸引， 在动脉壁模型中氧化，并且叶黄素补充减少了 动脉粥样硬化程度降低86%。此外， 补充剂中的维生素C与 颈动脉IMT进展。相反，从食物中摄入更多的维生素C 与颈动脉IMT进展减缓相关，但这种保护性 相关性不显著。HDL-C与IMT的保护关系 通过更高的血浆β-隐黄素和通过增加的血浆β-隐黄素水平来增强 一种破坏氧化脂质的酶（对氧磷酶）。 本申请建议继续观察LAAS队列， 增加了两种动脉功能障碍的超声测量方法， 实验室检查提示哮喘新病因探讨 的合作者。额外的观察也将增加 检测与IMT的关系。新的风险因素集中在以下途径， 促进或抑制动脉壁中的LDL损伤和炎症反应。 动脉功能和功能障碍的新措施是（1）内皮 肱动脉功能（管腔直径增加， 充血）;和（2）颈总动脉的扩张性或僵硬。 这些补充措施连同原议定书中的措施将 允许研究Ath的纵向变化与饮食 抗氧化剂、抗氧化酶和遗传多态性。