Altered elastase—alpha1-antitrypsin balance in the blood of patients with chronic venous disease

Abstract

Objectives

Although leukocyte elastase is suspected to be involved in the damage of vein wall during chronic venous disease, the equilibrium between this protease and its inhibitor, alpha1-antitrypsin, has not yet been evaluated. The aim of the present study was to determine the relationship between leukocyte elastase and alpha1-antitrypsin, in the blood of patients with chronic venous disease.

Patients and methods

The concentration and the activity of leukocyte elastase along with the activity of alpha1-antitrypsin were evaluated in the blood of 55 chronic venous disease patients. The results were compared with those obtained in 33 healthy age and sex-matched volunteers.

Results

A significant decrease in the leukocyte elastase activity that correlated with an increased alpha1-antitrypsin activity was observed in the serum of patients with mild clinical symptoms of chronic venous disease.

Conclusions

The results of the study did not confirm a hypothesis about an important role of proteolytic activity of leukocyte elastase in the vein wall injury mechanism. They show that the leukocyte elastase–alpha1-antitrypsin balance is rather shifted toward antiprotease activity, especially in an early stage of chronic venous disease.

Keywords

Chronic venous disease varicose veins elastase alpha1-antitrypsin

Get full access to this article

View all access options for this article.

References

Smith

. Neutrophil activation and mediators of inflammation in chronic venous insufficiency. J Vasc Surg 1999; 36: 24–36.

Stvrtinova

Jahnova

Weissova

. Inflammatory mechanisms involving neutrophils in chronic venous insufficiency of lower limbs. Bratisl Lek Listy 2001; 102: 235–239.

Smith

. Update on chronic venous insufficiency induced inflammatory processes. Angiology 2001; 52: S35–S42.

Stvrtinova

Ferencikova

. Lysosomal enzymes and superoxide production in polymorphonuclear leukocytes of patients with primary varicose veins. Cor Vasa 1992; 34: 255–264.

Shields

Andaz

Sarin

. Plasma elastase in venous diseases. Br J Surg 1994; 81: 1496–1499.

Tetley

. New perspectives on basic mechanisms in lung disease. 6. Proteinase imbalance: its role in lung disease. Thorax 1993; 48: 560–565.

Decock

Paridaens

Cufer

. Proteases and metastasis: clinical relevance nowadays? Curr Opin Oncol 2005; 17: 545–550.

Hiemstra

. Novel roles of protease inhibitors in infection and inflammation. Biochem Soc Trans 2002; 30: 116–120.

Franck

Byrjalsen

. A simple and sensitive chromogen assay for the measurement of elastase-type enzyme activity in human plasma. Biol Chem Hoppe-Seyler 1988; 396: 677–682.

10.

Hallar

Broemstrup

Kantari

. Structure of human proteinase 3 and neutrophil elastase—so similar yet so different. FEBS J 2010; 277: 2238–2254.

11.

Lee

Downey

. Leukocyte elastase. Physiological function and role in acute lung injury. Am J Respir Crit Care Med 2001; 164: 896–904.

12.

Wulfsberg

Hoffman

Cohen

. Alpha-1-antitrypsin deficiency: impact of genetic discovery on medicine and society. JAMA 1994; 271: 217–222.

13.

Fregonese

Stolk

. Hereditary alpha-1-antitrypsin deficiency and its clinical consequences. Orphanet J Rare Dis 2008; 3: 16.

14.

Owen

Campbell

. The cell biology of leukocyte-mediated proteolysis. J Leukocyt Biol 1999; 65: 137–150.

15.

Cohen

Mandell

Margolis

. Altered aortic protease and antiprotease activity in patients with ruptured abdominal aortic aneurysms. Surg Gynecol Obstet 1987; 164: 355–358.

16.

Baker

Fiore

Connolly

. Serum elastase and alpha-1-antitrypsin levels in patients with ruptured and unruptured cerebral aneurysms. Neurosurgery 1995; 37: 56–61.

17.

Gadek

Pacht

. The protease-antiprotease balance within the human lung: implication for the pathogenesis of emphysema. Lung 1990; 168: 552–564.

18.

Sun

Yang

. Role of imbalance between neutrophil elastase and alpha-1-antitrypsin in cancer development and progression. Lancet Oncol 2004; 5: 182–190.

19.

Bujan

Gimeno

Jimenez

. Expression of elastin components in healthy and varicose veins. Word J Surg 2003; 27: 901–905.

20.

Paczek

Michalska

Bartłomiejczyk

. Trypsin, elastase, plasmin and MMP-9 activity in the serum during the human ageing process. Age Ageing 2008; 37: 318–323.

21.

Grinnell

Zhu

. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1-proteinase inhibitor and alpha2-macroglobulin. J Invest Dermatol 1996; 106: 335–341.

22.

Chen

Ward

Olutove

. Ability of chronic wound fluids to degrade peptide growth factor is associated with increased levels of elastase activity and diminish levels of proteinase inhibitors. Wound Repair Regen 1997; 5: 23–32.

23.

Kowalewski

Sobolewski

Wolanska

. Matrix metalloproteinase in the vein wall. Int Angiol 2004; 23: 164–169.

24.

Woodside

Burke

. Morphologic characteristics of varicose veins: possible role of metalloproteinases. J Vasc Surg 2003; 38: 162–169.

25.

Rayment

Upton

Shooter

. Increased matrix metalloproteinase-9 (MMP-9) activity observed in chronic wound fluid is related to the clinical severity of ulcers. Br J Dermatol 2008; 158: 951–961.

26.

Gandhi

Irizarry

Nackman

. Analysis of the connective tissue matrix and proteolytic activity of primary varicose veins. J Vasc Surg 1993; 18: 814–820.

27.

Weckroth

Vaheri

Lauharanta

. Matrix metalloproteinases, gelatinase and collagenase, in chronic leg ulcers. J Invest Dermatol 1996; 106: 1199–1124.

28.

Wali

Eid

. Inimal changes in varicose veins: an ultrastructural study. J Smooth Muscle Res 2002; 38: 63–74.

29.

Jeannert

Baldi

Heilemariam

. Selectively loss of extracellular matrix proteins is linked to the biophysical properties of varicose veins assessed by ultrasonography. Br J Surg 2007; 94: 449–456.

30.

Elsharawy

Naim

Abdelmaguid

. Role of saphenous vein wall in the pathogenesis of varicose veins. Interact Cardiovasc Thorac Surg 2007; 6: 219–224.

31.

Davies

Magee

Baird

. Pre-bypass morphological changes in vein grafts. Eur J Vasc Surg 1993; 7: 642–647.

32.

Jacob

Cazaubon

Scemama

. Plasma matrix metalloproteinase-9 as a marker of blood stasisin varicose veins. Circulation 2002; 106: 535–538.

33.

Ikeda

Kambavashi

Iwamoto

. The coagulofibrinolytic state of patients with primary varicose veins of lower legs. Surg Today 1996; 26: 985–989.

34.

Dzieciuchowicz

Espinosa

Paramo

. Increased levels of metalloproteinase 10 and hemostatic markers in patients with noncomplicated primary varicose veins. Clin App Thromb Hemost 2014, pp. Epub, DOI: 10:1076029613517167.

35.

Guzik

Chwała

Matusik

. Mechanisms of increased vascular superoxide production in human varicose veins. Pol Arch Med Wewn 2011; 121: 279–286.

36.

Yasim

Kilinc

Aral

. Serum concentration of procoagulant, endothelial and oxidative stress markers in early primary varicose veins. Phlebology 2008; 23: 15–20.

37.

Tisato

Zauli

Gianesini

. Modulation of circulating cytokine-chemokine profile in patients affected by chronic venous insufficiency undergoing surgical hemodynamic correction J Immunol Res 2014; 2014: 473765.

38.

Signorelli

Malaponte

Di Pino

. Venous stasis causes release of interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) by monocyte-macrophage. Clin Hemorheol Microcirc 2000; 22: 311–316.

39.

Blomgren

Johansson

Siegbahn

. Coagulation and fibrinolysis in chronic venous insufficiency. Vasa 2001; 30: 184–187.

40.

Parra

Cambria

Hower

. Tissue inhibitor of metalloproteinase-1 is increased in saphenofemoral junction of patients with varices in the leg. J Vasc Surg 1998; 28: 669–675.

41.

Badier-Commander

Verbueren

Lebard

. Increased TIMP/MMP ratio in varicose veins: a possible explanation for extracellular matrix accumulation. J Pathol 2000; 192: 105–112.

42.

Shamamian

Schwartz

Pocock

. Activation of progelatinase A (MMP-2) by neutrophil elastase, cathepsin G and proteinase-3: a role for inflammatory cells in tumor invasion and angiogenesis. J Cell Physiol 2001; 189: 197–206.

43.

Okada

Nakanishi

. Activation of matrix metalloproteinase 3 (stromelysin) and matrix metalloproteinase 2 (gelatinase) by human neutrophil elastase and cathepsin G. FEBS Lett 1989; 249: 353–356.

44.

Ferry

Lonchampt

Pennel

. Activation of MMP-9 by neutrophil elastase in an in vivo model of acute lung injury. FEBS Lett 1997; 402: 111–115.

45.

Chello

Mastroroberto

Romano

. Alteration in collagen and elastin content in varicose veins. Vasc Endovasc Surg 1994; 28: 23–27.

46.

Aunapuu

Arend

. Histopathological changes and expression of adhesion molecules and laminin in varicose veins. Vasa 2005; 34: 170–175.

47.

Kirsch

Dienes

Kuchle

. Changes in the extracellular matrix of the vein wall—the cause of primary varicosis? Vasa 2000; 29: 173–177.

48.

Rose

Ahmed

. Some thoughts of the aetiology of varicose veins. J Cardiovasc Surg 1986; 27: 534–543.