Title:Matrix Metalloproteinases as Potential Targets in the Venous Dilation Associated with Varicose Veins
Volume: 14
Issue: 3
Author(s): Arda Kucukguven and Raouf A. Khalil
Affiliation:
Keywords:
MMP, endothelium, vascular smooth muscle, extracellular matrix, chronic venous insufficiency disease, TIMP, Varicose Veins, collagen, THROMBOPHLEBITIS, APOPTOSIS
Abstract: Varicose veins (VVs) are a common venous disease of the lower extremity characterized by incompetent
valves, venous reflux, and dilated and tortuous veins. If untreated, VVs could lead to venous thrombosis, thrombophlebitis
and chronic venous leg ulcers. Various genetic, hormonal and environmental factors may lead to structural changes in the
vein valves and make them incompetent, leading to venous reflux, increased venous pressure and vein wall dilation. Prolonged
increases in venous pressure and vein wall tension are thought to increase the expression/activity of matrix metalloproteinases
(MMPs). Members of the MMPs family include collagenases, gelatinases, stromelysins, matrilysins, membrane-
type MMPs and others. MMPs are known to degrade various components of the extracellular matrix (ECM). MMPs
may also affect the endothelium and vascular smooth muscle, causing changes in the vein relaxation and contraction
mechanisms. Endothelial cell injury also triggers leukocyte infiltration, activation and inflammation, which lead to further
vein wall damage. The vein wall dilation and valve dysfunction, and the MMP activation and superimposed inflammation
and fibrosis would lead to progressive venous dilation and VVs formation. Surgical ablation is an effective treatment for
VVs, but may be associated with high recurrence rate, and other less invasive approaches that target the cause of the disease
are needed. MMP inhibitors including endogenous tissue inhibitors (TIMPs) and pharmacological inhibitors such as
zinc chelators, doxycycline, batimastat and marimastat, have been used as diagnostic and therapeutic tools in cancer, autoimmune
and cardiovascular disease. However, MMP inhibitors may have side effects especially on the musculoskeletal
system. With the advent of new genetic and pharmacological tools, specific MMP inhibitors with fewer undesirable effects
could be useful to retard the progression and prevent the recurrence of VVs.
