Document Detail


Matrix metalloproteinases as potential targets in the venous dilation associated with varicose veins.
MedLine Citation:
PMID:  23316963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Arda Kucukguven; Raouf A Khalil
Related Documents :
8138853 - Progression of chronic obstructive pulmonary disease after multiple episodes of an occu...
21986623 - Asynchronous arterial systolic expansion as a marker of vascular aging: assessment of t...
11553223 - German experience with colon interposition grafting as an esophageal substitute.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current drug targets     Volume:  14     ISSN:  1873-5592     ISO Abbreviation:  Curr Drug Targets     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-27     Completed Date:  2013-08-14     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  100960531     Medline TA:  Curr Drug Targets     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  287-324     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Cell Movement
Dermatitis / drug therapy,  enzymology
Dilatation, Pathologic
Female
Humans
Hydrostatic Pressure
Male
Matrix Metalloproteinase Inhibitors / therapeutic use*
Matrix Metalloproteinases / physiology*
Scleroderma, Localized / drug therapy,  enzymology
Thrombophlebitis / drug therapy,  enzymology
Varicose Veins / complications,  drug therapy*,  enzymology,  etiology
Vasoconstriction
Wound Healing
Grant Support
ID/Acronym/Agency:
HL-65998/HL/NHLBI NIH HHS; HL-98724/HL/NHLBI NIH HHS; R01 HL065998/HL/NHLBI NIH HHS; R21 HL098724/HL/NHLBI NIH HHS; R21 HL111775/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Matrix Metalloproteinase Inhibitors; EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Matrix metalloproteinases: drug targets for myocardial infarction.
Next Document:  Matrix metalloproteinases as drug targets in preeclampsia.