Responsivity of homocysteine to behavioral stress

说明(申请人提供)：同型半胱氨酸是冠心病(CHD)的潜在危险因素。它是一种与内皮损伤相关的氨基酸，可直接损伤内膜细胞，并有助于动脉粥样硬化病变中脂蛋白的沉积。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，但关于心理危险因素和同型半胱氨酸的研究很少。我们已经证明，同型半胱氨酸在应激时增加，敌意与休息时的同型半胱氨酸呈正相关。这项建议的主要目的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；评估应激过程中血脂和同型半胱氨酸的关系；并测试同型半胱氨酸反应的一种可行机制。研究1将通过比较患冠心病风险高于平均水平的人(基于美国心脏协会/美国心脏病学会的建议和家族史)和低于平均风险的人，来测试与压力相关的同型半胱氨酸增加是否具有病因学意义。这项研究还将建立在我们早期发现的基础上，通过比较高敌意个体和低敌意个体的同型半胱氨酸反应性。研究2将测试同型半胱氨酸反应性过度的个体是否比同型半胱氨酸反应性较低的个体在应激诱导的维生素B6、维生素B12和叶酸方面有更大的变化。这项研究的另一个目的是测试在急性应激源之前服用B族维生素补充剂4周的人，与服用安慰剂的人相比，压力诱导的同型半胱氨酸是否显示出较小的升高。由于同型半胱氨酸与脂蛋白结合，而且它似乎可以改变低密度脂蛋白的致动脉粥样硬化能力，这两项研究都将测试同型半胱氨酸与脂类反应性之间的关系。这项研究的结果将扩展现有但有限的数据，测试压力和敌意对同型半胱氨酸浓度的影响；将允许对与应激相关的同型半胱氨酸升高的病因学意义进行一次测试；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；并将测试同型半胱氨酸升高的可行机制。

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.