Responsivity of homocysteine to behavioral stress

同型半胱氨酸对行为压力的反应

• 批准号: 6542441
• 负责人: Catherine M Stoney
• 金额: $ 36.88万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-10 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6542441
• 关键词: aminoacid metabolism; atherosclerosis; behavioral /social science research tag; blood lipoprotein; cardiovascular disorder risk; catecholamines; clinical research; coronary disorder; dietary control; disease /disorder etiology; folate; homocysteine; human middle age (35-64); human subject; patient oriented research; personality; psychological stressor; psychosomatic disorders; social psychology; stress; vitamin B12; vitamin B6

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，可能导致内膜细胞直接损伤并有助于脂蛋白在动脉粥样硬化病变内沉积。同型半胱氨酸与脂蛋白结合。虽然一些心理特征与冠心病有关，但很少有关于心理危险因素和同型半胱氨酸的研究。我们已经证明，同型半胱氨酸在压力下增加，敌意与静息同型半胱氨酸呈正相关。本提案的主要目标是调查应激诱导和个性相关的同型半胱氨酸升高的病因学意义;评估应激期间脂质和同型半胱氨酸之间的关系;并测试同型半胱氨酸反应性的一种可行机制。研究1将通过比较高于CHD平均风险的个体（基于美国心脏协会/美国心脏病学会的建议和家族史）与低于平均风险的个体来测试与同型半胱氨酸相关的增加是否具有病因学意义。这项研究也将建立在我们早期的研究结果，通过比较高敌意个体和低敌意个体之间的同型半胱氨酸反应性。研究2将测试具有夸大的同型半胱氨酸反应性的个体是否比具有较小同型半胱氨酸反应性的个体在维生素B6、维生素B12和叶酸方面具有更大的应激诱导的改变。本研究的另一个目的是测试在急性应激源之前给予B族维生素补充剂4周的个体相对于给予安慰剂的个体是否显示出应激诱导的同型半胱氨酸的较小升高。因为同型半胱氨酸与脂蛋白结合，并且因为它似乎改变了低密度脂蛋白的致动脉粥样硬化性，所以两项研究都将测试同型半胱氨酸与脂质反应性之间的关系。这项研究的结果将扩展现有的，但有限的数据测试压力和敌意对同型半胱氨酸浓度的影响，将允许一个测试的病因学意义的压力相关的同型半胱氨酸升高，将使我们能够检查脂质反应性和同型半胱氨酸反应性之间的关系，并将测试一个可行的机制同型半胱氨酸升高。