Inflammation in venous disease.
Chronic venous disease (CVD), mainly due to venous reflux or, sometimes, to venous outflow obstruction, produces a microcirculatory overload leading to the impairment of venous drainage. Venous drainage depends primarily on a major hemodynamic parameter called trans-mural pressure (TMP). TMP is increased in patients affected by CVD, leading to impaired tissue drainage, and, consequently, facilitating the beginning of the inflammatory cascade. Increased TMP determines red blood cell extravasation and either dermal hemosiderin deposits or iron laden-phagocytes. Iron deposits are readily visible in the legs of all patients affected by severe CVD. Local iron overload could generate free radicals or activate a proteolytic hyperactivity of metalloproteinases (MMPs) and/or downregulate tissue inhibitors of MMPs. These negative effects are particularly evident in carriers of the common HFE gene's mutations C282Y and H63D, because intracellular iron deposits of mutated macrophages have less stability than those of the wild type, inducing a significant oxidative stress. It has been demonstrated that such genetic variants increase the risk of ulcers and advance the age of ulcer onset, respectively. The iron-dependent vision of inflammation in CVD paves the way to new therapeutic strategies including the deliberate induction of iron deficiency as a treatment modality for non-healing and/or recurrent venous leg ulcers. The inflammatory cascade in CVD shares several aspects with that activated in the course of multiple sclerosis, an inflammatory and neurodegenerative disease of unknown origin in which the impairment of cerebral venous outflow mechanisms has been recently demonstrated.
Zamboni
P
P
Department of Surgery, Vascular Diseases Center, University of Ferrara, Ferrara, Italy. zmp@unife.it
Lanzara
S
S
Mascoli
F
F
Caggiati
A
A
Liboni
A
A
D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D019190:Iron Overload / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014680:Veins; D014690:Venous Pressure / Q000502:physiology