Pathophysiology of chronic venous insufficiency

Objective: To review the physiological mechanisms determining venous return to the heart and the pathophysiological events culminating in chronic venous insufficiency (CVI), focusing primarily on the role of alterations in nitric oxide (NO) production by the vascular endothelium. Background: Congenital valve incompetence, thrombotic damage or venous outflow obstruction result in the development of chronic venous hypertension which frequently leads to ulceration. One major aetiological factor of trophic changes in the skin of patients with CVI is the phenomenon of leucocyte trapping. Hypothesis: It has been suggested that endothelial dysfunction, effectively resulting in a decrease in cellular levels of NO, is a key event in the initiation of enhanced adhesion molecule expression. Data: P-selectin, monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 expression can be enhanced by attenuating endothelial NO production. The mechanism by which NO alters the expression of genes encoding these adhesion molecules would appear to involve an interaction with transcription factors, in particular NF kappa B. Conclusion: Impaired endothelial NO synthesis associated with CVI may enhance the expression of adhesion molecules and chemotactic factors and lead to leucocyte adhesion and extravasation.