Neutrophil Activation and Mediators of Inflammation in Chronic Venous Insufficiency

Abstract

The effect of venous hypertension on the state of activation of leucocytes has been investigated in patients with venous disease and control subjects. Leucocytes become ‘trapped’ in the circulation of the leg during periods of venous hypertension produced by sitting or standing. This is greater in the limbs of patients with chronic venous disease than controls. Studies of the plasma levels of neutrophil granule enzymes show that these are increased during periods of venous hypertension, suggesting that this causes activation of the neutrophils. Investigation of the leucocyte surface ligand CD11b shows that the more activated neutrophils and monocytes are sequestered during venous hypertension. Measurement of plasma levels of the soluble parts of the vascular (VCAM), intercellular (ICAM) and endothelial leucocyte (ELAM) adhesion molecules show that these are all elevated in patients with chronic venous disease compared to controls. Following 30 min of venous hypertension produced by standing, these levels are further increased. These data suggest that venous hypertension causes neutrophil and monocyte activation, which in turn causes injury to the endothelium. I believe that this may be the mechanism that initiates the pathological processes which lead to venous ulceration. It has recently been shown that the venotonic drug Daflon 500 mg (450 mg diosmin, 50 mg hesperidin, Servier, France) influences these processes. Surface expression of CD62L is reduced in neutrophils and monocytes, and plasma levels of soluble endothelial adhesion molecules are reduced. These observations may explain the anti-inflammatory effects of Daflon 500 mg.

The inflammatory reaction during chronic venous disease of lower limbs.

“…Attention has focused on the role of leukocytes in the pathophysiology of changes of the venous wall structure. The intense leukocytes infiltration, mainly macrophages and lymphocytes in CVD patients was observed [28]. The amounts of granulocytes, monocytes, macrophages and T lymphocytes increased in the venous wall of veins with the elevation of the blood pressure [29].…”

Venous Hypoxia: A Poorly Studied Etiological Factor of Varicose Veins

“…Venous stasis may cause oxidative stress by initiating a series of haemodynamic, metabolic, and nutritional changes including tissue hypoxia [31,32,33]. In a study of 45 patients with varicosities, downregulation of cytochrome-oxidase C and increased pyruvate expression in varicose compared to non-varicose portions of the veins suggested a reduction in oxidative phosphorylation in varicose veins [34].…”

“…Elevated oxidative stress has been associated with vein wall injury and chronic venous insufficiency (CVI) [31,32,33,37]. Moreover, leucocytes in the blood of varicose veins demonstrated increased oxidative stress compared with arm veins in patients with CVI [38,39].…”

Enhanced oxidative stress in workers with a standing occupation: Table 1

“…Table 1 Mean (SD) with 95% CI of venous pressure (VP) in both limbs and reactive oxygen metabolites (ROS) before and after work in the two groups; the mean percentage changes between pre-work and after-work level in the two groups are also shown evolution of CVI. [1][2][3] Among the mediators of vessel wall damage, ROS play an important role, acting through two main mechanisms. The first is the oxidation of cell membrane components, followed by endothelium damage, which eventually leads to increased vascular permeability.…”