Responsivity of homocysteine to behavioral stress

同型半胱氨酸对行为压力的反应

基本信息

批准号：
6921438
负责人：
CHARLES FISKE EMERY
金额：
$ 36.88万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-08-10 至 2007-07-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): Homocysteine is putative risk factor for coronary heart disease (CHD). It is an amino acid associated with endothelial damage, which may cause direct injury to intimal cells and assist in the deposition of lipoproteins within atherosclerotic lesions. Homocysteine is bound to lipoproteins. Although several psychological characteristics are associated with CHD, few investigations of psychological risk factors and homocysteine exist. We have shown that homocysteine increases during stress, and that hostility is positively associated with resting homocysteine. The major goals of this proposal are to investigate the etiological significance of stress-induced and personality-associated elevations in homocysteine; to evaluate the relationship between lipids and homocysteine during stress; and to test one viable mechanism for homocysteine reactivity. Study 1 will test whether the stress-associated increases in homocysteine are etiologically meaningful, by comparing individuals with above average risk for CHD (based on American Heart Association/American College of Cardiology recommendations and family history), to those at below average risk. This study will also build on our earlier findings, by comparing homocysteine reactivity among high hostile individuals to low hostile individuals. Study 2 will test whether individuals with exaggerated homocysteine reactivity have greater stress-induced alterations in vitamin B6, vitamin B12, and folate than do those with smaller homocysteine reactivity. An additional purpose of this study will be to test whether individuals given B vitamin supplements for 4 weeks prior to an acute stressor display smaller elevations in stress-induced homocysteine, relative to individuals given placebo. Because homocysteine is bound to lipoproteins, and because it appears to modify the atherogenicity of low density lipoprotein, both studies will test the relationships between homocysteine and lipid reactivity. The results of this research will extend the available but limited data testing the impact of stress and hostility on homocysteine concentrations; will allow one test of the etiological significance of stress-related homocysteine elevations; will allow us to examine the relationship between lipid reactivity and homocysteine reactivity; and will test a viable mechanism for the homocysteine elevations.

描述（由申请人提供）：同型半胱氨酸是冠心病（CHD）的假定危险因素。它是一种与内皮损伤相关的氨基酸，可能会导致内膜细胞直接损伤，并有助于在动脉粥样硬化病变中沉积脂蛋白。同型半胱氨酸注定为脂蛋白。尽管几种心理特征与冠心病有关，但对心理危险因素和同型半胱氨酸的研究很少。我们已经表明，在压力期间，同型半胱氨酸增加，并且敌对情绪与静息同型半胱氨酸呈正相关。该提案的主要目标是研究压力诱导和人格相关的同型半胱氨酸的病因学意义。评估压力期间脂质与同型半胱氨酸之间的关系；并测试一种可行的同型半胱氨酸反应性的机制。研究1将通过比较具有高于平均风险的CHD风险的个体（基于美国心脏协会/美国心脏病学建议和家族病史）的人，测试同型半胱氨酸的压力相关的增加在病因上是有意义的。这项研究还将通过将高敌对个体的同半胱氨酸反应性与低敌对个体进行比较，以我们的早期发现为基础。研究2将测试夸张的同型半胱氨酸反应性的个体是否比具有较小的同型半胱氨酸反应性的人更大，维生素B6，维生素B12和叶酸的变化更大。这项研究的另一个目的是在急性应激源显示在应力诱导的同型半胱氨酸的急性应激素之前测试个人是否给予B维生素补充剂，相对于给定安慰剂的个体显示出较小的升高。由于同型半胱氨酸势必会脂蛋白，并且由于它似乎可以改变低密度脂蛋白的动脉粥样硬化性，因此两项研究都将测试同型半胱氨酸和脂质反应性之间的关系。这项研究的结果将扩大可用但有限的数据测试，从而将压力和敌意对同型半胱氨酸浓度的影响。将允许对与压力相关的同型半胱氨酸升高的病因学意义进行一项测试；将使我们能够检查脂质反应性与同型半胱氨酸反应性之间的关系；并将测试同型半胱氨酸抬高的可行机制。