RESPONSIVITY OF HOMOCYSTEINE TO BEHAVIORAL STRESS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。主要问题和回答变量：1.探讨应激相关同型半胱氨酸变化在冠心病发病机制中的意义。(研究1)为了实现这一目标，我们计划比较高风险个体和低风险个体在应激过程中的同型半胱氨酸(Hcy)浓度。我们先前的数据显示，在一小部分中年女性的心理应激期间，Hcy浓度显著且短暂地升高。我们之前的数据还表明，敌意高的健康男性和女性在休息时的同型半胱氨酸浓度比敌意低的人高。2.测试应激相关同型半胱氨酸升高的机制。(研究2)为了实现这一目标，我们将确定压力期间Hcy短期上升的一个机制是否是维生素B6、维生素B12和/或叶酸的急剧下降。慢性应激会导致B6缺乏，而在正常范围内类似的缺乏会导致消极的情感状态，如易怒和抑郁。B6是同型半胱氨酸转化为半胱氨酸的重要辅因子，而这些B族维生素的慢性改变是同型半胱氨酸最重要的决定因素。3.探讨应激诱导的同型半胱氨酸变化与脂蛋白的关系。(研究1和2)我们长期以来一直有兴趣了解脂蛋白对心理应激源的反应模式和机制。因为同型半胱氨酸与脂蛋白结合，而且似乎可以改变低密度脂蛋白的致动脉粥样硬化能力，所以我们将测试同型半胱氨酸与脂质反应性之间的关系。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Primary Question and Response Variable: 1.To investigate the significance of stress-related homocysteine changes in the etiology of CHD. (Study 1)To accomplish this aim, we plan to compare homocysteine (Hcy) concentrations during stress in high- and low-risk individuals. Our previous data demonstrated that Hcy concentrations rose significantly and transiently during psychological stress in a small sample of middle-aged women. Our previous data also indicated that healthy men and women high in hostility had higher Hcy concentrations at rest that did those low in hostility. 2.To test a mechanism for the stress-associated homocysteine increases. (Study 2)To accomplish this goal, we will determine if one mechanism for the short-term rise in Hcy during stress is an acute decline in vitamin B6, vitamin B12, and/or folate. Chronic stress results in B6 deficiency, and similar deficiencies within the normal ranges induce negative affective states such as irritability and depression. B6 is an essential cofactor in the trassulfuration of Hcy to cystine, and chronic alterations in these B vitamins are the most important determinants of Hcy. 3.To examine the relationship between stress-induced changes in homocysteine and lipoproteins. (Studies 1 & 2) We have a long-standing interest in understanding the patterns and mechanisms of lipoprotein reactivity to psychological stressors. Because Hcy is bound to lipoproteins, and because it appears to modify the atherogenicity of LDL, we will test the relationships between Hcy and lipid reactivity.