Objective: Hyperhomocysteinemia and hypertriglyceridemia are independently associated with atherosclerotic disease. The process of atherogenesis involves inflammation and endothelial dysfunction. We tested whether concurrent acute hyperhomocysteinemia and mild hypertriglyceridemia increase the concentrations of circulatory cellular adhesion molecules in healthy subjects.
Study design and methods: Twelve healthy volunteers aged 37.5 years (range, 25-51) participated in the present study. The concentrations of plasma total homocysteine (p-tHcy), serum triglycerides, circulatory cellular adhesion molecules (CAMs), and concentrations of nitrate were measured at 0 (fasting), 2, 4, and 6 h after loading with (1) methionine, (2) fat, (3) methionine + fat, and (4) water (control). Wash out period between each loading was >or=1 week.
Results: Percent relative changes from baseline in the concentrations of p-tHcy, 2, 4, and 6 h after methionine and methionine + fat were significantly different from after water and fat loading. Changes in the concentrations of serum triglycerides 2 h after fat loading were significantly different from water loading, whereas methionine + fat loading caused a significant difference after 2, 4, and 6 h. We detected a synergistic increase in the triglyceride area response to methionine + fat loading. We detected also a significant difference in percent relative changes in the concentrations of P-selectin (PSEL) (P = 0.02), E-selectin (ESEL) (P = 0.003), and vascular cell adhesion molecule-1 (VCAM-1) (P = 0.005) 6 h after methionine + fat loading as compared to water loading. There was an additive increase in the PSEL area response to methionine + fat loading. Furthermore, area response to VCAM was greater to methionine loading than water loading (P = 0.01). A decrease in the concentration of NO(3) was more pronounced after methionine + fat loading and a significantly decreased area response of nitrate to methionine + fat loading was detected than to area response to water loading (P = 0.002).
Conclusion: Inflammatory activation of the endothelium takes place during concurrent transient hyperhomocysteinemia and mild hypertriglyceridemia.