Von Willebrand Factor, C-reactive Protein, Nitric Oxide, and Vascular Endothelial Growth Factor in a Dietary Reversal Model of Hypercholesterolemia in Rabbit

Aims: Endothelial dysfunction is considered a sign of the early vascular changes preceding atherosclerosis. We studied the alteration of von Willebrand Factor (vWF), C - reactive protein (CRP), nitrite and Vascular Endothelial Growth Factor (VEGF) in a dietary reversal model of hypercholesterolemia in rabbit.

Methods: This project was designed in two phases. In phase I, male rabbits (n = 11) were fed a 1% high cholesterol diet for 30 days. Then the diet was replaced with normal rabbit chow for other 30 days (cholesterol withdrawal phase, phase II). To compare the fatty streak formation with normal condition, a control group (n = 6) received normal diet during the study. The serum lipid levels, vWF, CRP, nitrite, and VEGF were measured before the experiment and by the end of each phase. Fatty streak formation in the walls of the aortas in both groups (high cholesterol diet and control group) was determined using intima thickness/media thickness (IMT) ratio.

Results: The results indicate that the level of cholesterol, Low Density Lipoproteins (LDL), vWF and CRP increased significantly in phase I, and decreased after hypercholesterolemic diet withdrawal (p < 0.05). No statistically significant changes were found in VEGF levels but the serum level of nitrite increased significantly during both phases of the study (p < 0.05). The IMT ratio in the walls of aortas was significantly different between the groups in both phases of studies (p < 0.05). There was a significant correlation between nitrite and cholesterol levels in both phases (r = 0.62 and r = 0.98, p < 0.05). Nitrite concentration also correlated with IMT ratio in both phases of the study (r = 0.75 and r = -0.99, p < 0.05). vWF did not correlate with cholesterol but it correlated with IMT ratio in both phases of the study (r = 0.87 and r = 0.84, p < 0.05). CRP only correlated with cholesterol in the first phase (r = 0.91, p < 0.05).

Conclusions: Among the endothelial biomarkers, vWF was found to be a biological marker for identifying the risk of developing atherosclerosis; however a single biomarker may not provide appropriate information.