RESPONSIVITY OF HOMOCYSTEINE TO BEHAVIORAL STRESS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。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状态下的同型半胱氨酸（Hcy）浓度。我们之前的数据表明，在一小部分中年妇女中，Hcy浓度在心理压力期间显著且短暂地上升。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Hcy浓度高于敌意低的男性和女性。2.为了测试压力相关的同型半胱氨酸增加的机制。（研究2）为了实现这一目标，我们将确定在压力下Hcy短期上升的一种机制是否是维生素B6、维生素B12和/或叶酸的急性下降。慢性应激导致B6缺乏，在正常范围内类似的缺乏会导致烦躁和抑郁等负面情绪状态。B6是Hcy转化为胱氨酸的重要辅助因子，而这些B族维生素的慢性变化是Hcy的最重要决定因素。探讨应激诱导的同型半胱氨酸变化与脂蛋白之间的关系。（研究1和2）长期以来，我们一直对了解脂蛋白对心理压力源的反应模式和机制感兴趣。由于Hcy与脂蛋白结合，并且它似乎可以改变LDL的动脉粥样硬化性，因此我们将测试Hcy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.