Chronic Venous Disorders: The Dangerous, the Good, and the Diverse

Abstract

Chronic venous disorders are common vascular pathology of great medical and socioeconomic impact, characterized by a wide spectrum of clinical manifestations occurring with symptoms and/or signs that vary in type and severity. The predominant pathophysiological mechanisms of chronic venous disease start from the development of venous hypertension from shear stress and reflux, leading to endothelial dysfunction and venous wall dilatation. The altered hemodynamic transduces physical signals into harmful bio-molecular pathways, creating a vicious cycle among shear stress, proteolytic remodeling, and inflammatory processes. This intricate network is further exacerbated by the degradation of protective endothelial glycocalyx. In this special issue, at least three main aspects of these interactions are highlighted: the dangerous, the good, and the diverse, which may help to focus attention on the biomolecular mechanisms and the possible targeted therapy of chronic venous disorders (CVeD).

Keywords: biomarkers; chronic venous disorders; chronic venous insufficiency; cytokines; glycocalyx; glycosaminoglycan; inflammation; matrix metalloproteinases; venous leg ulcer; wound healing.

Figure 1

The Dangerous network of the complex mechanisms contributing to both initiation and progression of the different stages of CVeD.

Figure 2

Schematic representation of biomolecular transduction pathways related to the hypertensive hemodynamic alteration in early stages of CVeD and late steps of CVI (modified and adapted from ref. [4]).

Figure 3

Schematic representation of the ability of GAGs, like Janus Bifrons, to down-regulate the harmful inflammatory/proteolytic pathways (red T-bar) and to up-regulate the favorable anti-inflammatory/proteolytic cascade (green arrows) in venous microenvironment during the different stages of CVI. “Stall” represents the critical condition, like a “biological switch”, in which the chronic venous disorders may enter either in the inflammatory vicious cycle (recurrence of delayed healing of leg ulcers) or progress to the enhanced healing processes of the wounds.