Raffetto JD, Khalil RA, et al.
Vessel plus. Date of publication 2021 Jan 1;volume 5():.
1. Vessel Plus. 2021;5:36. doi: 10.20517/2574-1209.2021.16. Epub 2021 May 29.
Mechanisms of Lower Extremity Vein Dysfunction in Chronic Venous Disease and
Implications in Management of Varicose Veins.
Raffetto JD(1), Khalil RA(1).
Author information:
(1)Vascular Surgery Research Laboratories, Division of Vascular and Endovascular
Surgery, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Chronic venous disease (CVD) is a common venous disorder of the lower
extremities. CVD can be manifested as varicose veins (VVs), with dilated and
tortuous veins, dysfunctional valves and venous reflux. If not adequately
treated, VVs could progress to chronic venous insufficiency (CVI) and lead to
venous leg ulcer (VLU). Predisposing familial and genetic factors have been
implicated in CVD. Additional environmental, behavioral and dietary factors
including sedentary lifestyle and obesity may also contribute to CVD.
Alterations in the mRNA expression, protein levels and proteolytic activity of
matrix metalloproteinases (MMPs) have been detected in VVs and VLU. MMP
expression/activity can be modulated by venous hydrostatic pressure, hypoxia,
tissue metabolites, and inflammation. MMPs in turn increase proteolysis of
different protein substrates in the extracellular matrix particularly collagen
and elastin, leading to weakening of the vein wall. MMPs could also promote
venous dilation by increasing the release of endothelium-derived vasodilators
and activating potassium channels, leading to smooth muscle hyperpolarization
and relaxation. Depending on VVs severity, management usually includes
compression stockings, sclerotherapy and surgical removal. Venotonics have also
been promoted to decrease the progression of VVs. Sulodexide has also shown
benefits in VLU and CVI, and recent data suggest that it could improve venous
smooth muscle contraction. Other lines of treatment including induction of
endogenous tissue inhibitors of metalloproteinases (TIMPs) and administration of
exogenous synthetic inhibitors of MMPs are being explored, and could provide
alternative strategies in the treatment of CVD.
DOI: 10.20517/2574-1209.2021.16
PMCID: PMC8270011
PMID: 34250453
Conflict of interest statement: CONFLICT OF INTEREST None
