Serum iron and matrix metalloproteinase-9 variations in limbs affected by chronic venous disease and venous leg ulcers.
BACKGROUND
Severe chronic venous disease (CVD) is characterized by both dermal hemosiderin accumulation and matrix metalloproteinase (MMP) hyperactivation. The iron-driven pathway is one of the recognized mechanisms of MMP hyperactivation.


OBJECTIVE
To investigate the potential consequences of leg hemosiderin deposits on both iron metabolism and activation of MMPs.


METHODS
We contemporaneously assessed the following in the serum of the arm and ankle veins of 30 patients (C4-6) with CVD and 14 normal subjects: ferritin, transferrin, iron, percentage of transferrin iron binding capacity (%TIBC), and MMP-9. Optical microscopy examinations with Perls' staining of chronic wounds were also performed.


RESULTS
Histology consistently revealed iron deposits. Serum ferritin, iron, and %TIBC were significantly increased in the legs affected by severe CVD compared with the arm of the same subjects or the controls. In addition, iron and %TIBC were significantly elevated in the legs of ulcer patients. The rate of activation of MMP-9 was significantly elevated in CVD.


CONCLUSIONS
The increased iron deposition in legs affected by CVD seems to be more instable in ulcer patients, leading to iron release in the serum of the affected leg. Our data suggest the iron-driven pathway as a further mechanism for MMP hyperexpression leading to tissue lesion.
Inter-departmental Vascular Disease Center, university of Ferrara, Ferrara, Italy. zmp@unife.it
Paolo
P
Zamboni
Gianluigi
G
Scapoli
Vincenzo
V
Lanzara
Marcello
M
Izzo
Patrizia
P
Fortini
Rea
R
Legnaro
Annunziata
A
Palazzo
Silvia
S
Tognazzo
Donato
D
Gemmati
D002908:Chronic Disease; D005260:Female; D005293:Ferritins / Q000097:blood; D006242:Haptoglobins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000097:blood*; D007871:Leg Ulcer / Q000097:blood*; D008264:Macrophages / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D014168:Transferrin / Q000032:analysis; D014652:Vascular Diseases / Q000097:blood* / Q000503:physiopathology
D006242:Haptoglobins; D014168:Transferrin; D005293:Ferritins; D007501:Iron; D020780:Matrix Metalloproteinase 9