Where are Atherosclerosis and Hypertension Hiding? Location and Function of Indoleamine 2,3-dioxygenase in Vascular Tissue

Abstract

This study explored the role of the enzyme indoleamine 2,3-dioxygenase (IDO) in vascular tissue with the hopes of shedding some light on this enzyme's possible involvement in the development of atherosclerosis and/or hypertension, as recent research has suggested that IDO may play a role in causing inflammation or that some of its metabolites may affect blood pressure. We performed immunohistochemical staining and Western blot analysis on samples of aorta from normal, Sham, and D-OCA rats with anti-IDO antibody in order to locate IDO in the vasculature. We also performed contractility experiments on normal rat aorta tissue with a substrate, inhibitor, and multiple metabolites of IDO in order to determine how IDO activity affected contractility of the vasculature. The presence of IDO in normal, Sham, and DOCA samples was consistently found Western blot analysis, but not with immunohistochemistry. Densitometric analysis of Western blots showed expression of IDO in DOCA tissue to be significantly less than in Sham tissue (p<O.05). Contractility experiments showed that normal tissue response to the tested substrate, inhibitor, and metabolites was minimal. The immunohistochemistry results are puzzling and this experiment should be repeated, perhaps with a custom-made antibody. Also, a greater amount of samples should be tested with Western blot analysis to obtain a greater n value and come to a firmer conclusion about the relationship between hypertension and IDO expression. The contractility experiments should also be repeated, perhaps using higher concentrations. Future studies should explore the expression IDO in and contractility of tissues treated with interferon-gamma (IFN-𝛾) and/or tumor necrosis factor alpha (TNF-α), substances known to increase IDO expression. Investigation into the role of IDO is important not only in terms of hypertension and atherosclerosis, but it is also believed that the enzyme is of importance in illnesses such as depression, HIV, and coronary heart disease.