Plasminogen activation in venous leg ulcers

Herouy, Yared; Trefzer, D; Hellstern, Michael; Stark, G. B.; Vanscheidt, Wolfgang; Schöpf, Erwin; Norgauer, Johannes

doi:10.1046/j.1365-2133.2000.03825.x

Cited by 35 publications

(25 citation statements)

References 21 publications

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“…The regulation of MMP production and function, although not fully understood, is likely to be linked to cytokines, urokinase plasminogen activator, EMMPRIN (extracellular MMP inducer CD147), platelet-derived growth factor AA, and mitogen-activated protein kinase pathways. [71][72][73][74][75][76][77][78][79][80][81][82] Importantly, the mitogen-activated protein kinase pathways in venous ulcer fibroblast have been demonstrated to overexpress P38, a negative modulator of cell proliferation causing growth arrest, which can also be upregulated with the cytokines TNF-a and interleukin-1. The expression of P38 can be suppressed, leading to fibroblast growth, by treatment with fibroblast growth factor.…”

Section: Venous Anatomy and Pathophysiologymentioning

confidence: 97%

Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum

O’Donnell¹,

Passman²,

Marston³

et al. 2014

Journal of Vascular Surgery

576

450

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Section: Venous Anatomy and Pathophysiologymentioning

confidence: 97%

Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum

O’Donnell¹,

Passman²,

Marston³

et al. 2014

Journal of Vascular Surgery

576

450

View full text Add to dashboard Cite

“…The mRNA-expression of VEGF, Ang-1 and Ang-2, Tie-2, VEGF-R1 and VEGF-R2 was analysed semiquantitatively by reverse transcriptase-polymerase chain reaction (23). Briefly, total mRNA was prepared from tissue sections using an RNeasy kit (Qiagen, Hilden, Germany).…”

Section: Methodsmentioning

confidence: 99%

Inhibition of angiogenesis in lipodermatosclerosis: Implication for venous ulcer formation

Herouy¹

2009

Int J Mol Med

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Abstract. Lipodermatosclerosis refers to skin induration of the lower extremities characterized by tortous, hyperpermeable vessels preceding venous leg ulcerations. Protein ligands and receptor tyrosine kinases that specifically regulate endothelial cell function are mainly involved in physiological as well as in disease-related angiogenesis. These ligand/receptor systems include the vascular endothelial growth factor (VEGF) and the angiopoietin (Ang) families and their receptor the tyrosine kinase with immuno-

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“…This point is well illustrated by the absence of wound healing in varicose leg ulcers. Chronic leg ulcers are characterized by the presence of proteases, ie, elastase 125 and plasmin, 126 and of degraded antiproteases 127 as well as adhesive glycoproteins, such as fibronectin 128 and tenascin. 129 The release of proteinases, particularly elastase, by the chronic leg ulcer represents a poor prognosis for the cellular healing process.…”

Section: Involvement Of Anoïkis In Vascular Diseasementioning

confidence: 99%

Anoïkis in the Cardiovascular System

Michel

2003

ATVB

213

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Abstract-Anoïkis is defined as programmed cell death induced by the loss of cell/matrix interactions. Adhesion to structural glycoproteins of the extracellular matrix is necessary for survival of the differentiated adherent cells in the cardiovascular system, including endothelial cells, smooth muscle cells, fibroblasts, and cardiac myocytes. Adhesion is also a key factor for the differentiation of mesenchymal stem cells. In particular, fibronectin is considered a factor of survival and differentiation for many adherent cells. Adhesion generates cell tensional integrity (tensegrity) and repression of apoptotic signals, whereas detachment has the opposite effect. Anoïkis plays a physiological role by regulating cell homeostasis in tissues. However, anoïkis can also be involved in pathological processes, as illustrated by the resistance to anoïkis in cancer and its enhancement in degenerative tissue remodeling. Extracellular mediators of anoïkis include matrix retraction, leading to loss of tensegrity in fibroblasts, pharmacological disengagement of integrins by RGD-like peptides and fragments of fibronectin, and focal adhesion disassembly by fragments of thrombospondin, plasminogen activator-1, and high-molecular-weight kininogen. In addition to binding of the RGD peptide by integrins, the engagement of the heparin binding sites of adhesive glycoproteins with glycosaminoglycans on the cell surface is also involved in the prevention of cell detachment-induced apoptosis. Proteases able to degrade adhesive glycoproteins, such as fibronectin, induce anoïkis of vascular adherent cells. Active proteases can either be secreted directly by inflammatory cells, as elastase and cathepsin G by polymorphonuclear leukocytes, chymase and tryptase by mast cells, and granzymes by lymphocytes, or generated from circulating zymogens by activation in close contact with the cells. This is the case for the pericellular conversion of plasminogen to plasmin, which degrades fibronectin and induces anoïkis of smooth muscle cells. Involvement of proteases has also been proposed in the apoptotic response of cultured adherent cells to serum starvation. Anoïkis is probably involved in pathological remodeling of cardiovascular tissues, including cardiac myocyte detachment in heart failure, deendothelialization and plaque rupture in atherosclerosis, and smooth muscle cell disappearance in aneurysms and varicose veins. The absence of cell adhesion and growth resulting from cleavage of adhesive proteins also represents a major impediment to cellular healing, including the absence of cell recolonization of proteolytically injured tissue and the low efficacy of cell transplantation. However, the exact role of anoïkis in cardiovascular pathologies remains to be further defined. Key Words: cell adhesion Ⅲ smooth muscle cell Ⅲ endothelium Ⅲ apoptosis Ⅲ aneurysm T he term anoïkis (from the ancient Greek word for homelessness) was first proposed by Frish and Francis in 1994. 1 Anoïkis is defined as a process of programmed cell death induced by the loss ...

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Plasminogen activation in venous leg ulcers

Abstract: Our findings indicate venous leg ulcers to be characterized by elevated plasminogen activation, suggesting that this enzyme cascade plays a crucial part in maintaining proteolytic activity in venous leg ulcers.

Cited by 35 publications

References 21 publications

Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum

Management of venous leg ulcers: Clinical practice guidelines of the Society for Vascular Surgery® and the American Venous Forum

Inhibition of angiogenesis in lipodermatosclerosis: Implication for venous ulcer formation

Anoïkis in the Cardiovascular System

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