Faculty Bibliography

Although prior studies have implicated nitric oxide (NO), a molecular messenger, in the development and progression of atherosclerosis, most of these studies have centered on atherosclerotic plaques. The current investigation determines whether a correlation exists between the presence of altered levels of NO production by peripheral blood mononuclear cells (PBMCs) and atherosclerotic disease. Venous blood was collected from 8 surgical patients having severe peripheral vascular disease and 8 healthy controls. PBMCs were separated by gradient centrifugation, diluted to 10(5) cells per mL, and cultured. Lipopolysaccharide (LPS), at doses of 10, 25, and 50 ng/mL, was used to stimulate NO production. Total nitric oxide assay was performed to determine the levels of NO produced by PBMCs at 24 and 48 hours. When stimulated by LPS there was an increase in NO production in the PBMCs cultured from control as well as patient samples, as compared to basal NO levels. However, the data demonstrate a significant decrease in the nitric oxide production in the patients with atherosclerosis as compared to that in the control group (p < 0.05). The differential production of nitric oxide by PBMCs of patients with atherosclerotic disease and healthy controls not only suggests that it has a role in the pathogenesis of this disease but also underlines its systemic nature. Blood cells circulating in the body with altered levels of NO production could have profound effects in the microvascular environment mediating molecular pathways and signaling cascades that activate and augment atherosclerosis.