Experimental Models To Investigate Inflammatory Processes in Chronic Venous Insufficiency

Abstract

Chronic venous insufficiency (CVI) is characterized by leukocyte adhesion and infiltration, venous hypertension and dilatation, and valvular dysfunction. The fact that activated white cells can direct a powerful cytotoxic arsenal at parenchymal cells following their extravasation into the tissues led to the original proposal that leukocytes may play a causative role in the pathogenesis of venous disease. A large body of subsequent work indicates that white blood cells are indeed activated in CVI. However, identification of the factors responsible for initiating leukosequestration and activation in such disorders and determinination of whether these activated cells then contribute to the progression of venous disease have been hampered by the lack of appropriate animal models that accurately mimic the human condition. Tantalizing evidence suggesting that cyclical periods of ischemia and reperfusion (I/R) may occur in diseased regions of the skin is beginning to accumulate. As is the case with CVI, leukocyte infiltration is a prominent feature in I/R and activated neutrophils play a causative role in the reperfusion component of tissue injury via the targeted release of reactive oxygen metabolites and hydrolytic enzymes. In light of these considerations, many investigators have suggested that examining the mechanisms of I/R injury in skin and skeletal muscle, where ischemia is produced by arterial occlusion, may provide a relevant model for studying the pathogenesis of CVI. Others have suggested that venous occlusion may represent a more appropriate model, as this approach also produces the venous hypertension that is characteristic of the disease. The purpose of this review is to summarize the evidence pointing to the involvement of I/R and venous hypertension as causative factors in CVI-induced leukocyte recruitment. In addition, we will describe the evidence in favor of the view that white blood cells contribute to the pathogenesis of CVI. Finally, we will describe several different experimental models that have been used to examine the role of I/R-induced microvascular dysfunction as it may pertain to the development of CVI, together with a discussion of the relative advantages and limitations of the various models. Microcirculation (2000) 7, S13-S22.

Unexpected Death in Elephantiasis Due to an Abnormal Life‐Style

“…These findings indicate the presence of chronic venous congestion in the lower limbs. Ronald et al demonstrated that the continuous elevation of venous pressure would induce the inflammatory cell collections on the venous wall through the expression of endothelial cell adhesion molecules such as vascular cell adhesion molecules and intercellular adhesion molecule (ICAM)-1 (8). The accumulated inflammatory cells injured the venous wall, deteriorated the venous function, and finally led to venous insufficiency (1).…”

“…We theorized that both elevation of interstitial pressure derived from lymph stasis and the extrinsic obstruction of the venous cavity would cause chronic venous dysfunction, and finally lead to chronic venous insufficiency in the lower limbs of the victim. Moreover, in chronic venous insufficiency the inflammatory cells aggregating around the vessels are reported to disrupt the integrity of the microvascular barrier and lead to extravasation of fluid into the interstitial space (8).…”

MicroRNA Profiling in Great Saphenous Vein Tissues of Patients with Chronic Venous Insufficiency

“…pregnancy, and family history have been identified (Ruckley et al 2002;Carpentier et al 2004), the molecular mechanisms underlying the pathogenesis of this disease remains vague. Various theories, such as the hemodynamic alteration causing venous hypertension (Bergan et al 2008), the incompetence of the saphenous venous valves (Duran et al 2000), the leukocyte-trapping hypothesis (Korthuis and Unthank 2000) and the weak vein wall hypothesis (Meissner et al 2007) had been put forward to explain the pathogenesis of varicose veins and CVI. However, these theories might remain some uncertainties and had been conflicting with each other.…”