This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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