Involvement of proteolytic enzymes—plasminogen activators and matrix metalloproteinases—in the pathophysiology of pressure ulcers

Abstract

The role of matrix-degrading enzymes, particularly plasminogen activators and matrix metalloproteinases, in the acute wound healing response has been the focus of many scientific studies. Only recently have these classes of endogenously produced proteinases been studied with regard to their involvement in the chronic wound environment. Using both in situ histologic zymography and immunohistochemical techniques, we examined the distribution of plasminogen activators and matrix metalloproteinase in the granulation tissue of pressure ulcers. Using in situ histologic zymography, urokinase was found to be the predominant plasminogen activator activity in the chronic wound granulation tissue, with little or no tissue-type plasminogen activator activity. These results were confirmed with the use of immunohistochemical techniques. In contrast, tissue-type plasminogen activator was found to be constitutively expressed in normal skin. Levels of matrix metalloproteinases were also found to be elevated in the granulation tissue of pressure ulcers. Immunohistochemical localization of leukocyte-associated proteinases (PMN elastase and cathepsin G) suggested a highly inflamed environment within the pressure ulcer granulation tissue. These results suggest a highly proteolytic environment within the chronic wound.

Electrochemical and antimicrobial properties of diamondlike carbon-metal composite films

“…Silver may also possess anti-inflammatory properties; for example, studies have shown increased neutrophil apoptosis, reduced matrix metalloproteinase activity, reduced tumor necrosis factor-alpha levels, and more rapid healing in wounds dressed with silver [15][16][17][18][19]. Silver must be in a soluble, uncharged (Ag 0 ) or metallic (Ag +1 ) form to provide these biological effects [7].…”

Selective urokinase-type plasminogen activator (uPA) inhibitors. Part 3: 1-Isoquinolinylguanidines

“…1 An inhibitor of uPA may have a therapeutic role in disease situations where uPA-driven degradation of extracellular matrix, or uPA-dependent cell migration is thought to be important--including tumour growth, metastasis, angiogenesis and chronic wounds. [2][3][4][5][6][7] The closely related enzyme tPA also acts via activation of plasminogen to plasmin and is a key component of the fibrinolytic cascade. 8;9 Achievement of adequate selectivity over both tPA and plasmin is therefore an important requirement in a therapeutically valuable uPA inhibitor.…”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Among possible causes for such impaired healing is the persistent inflammation within the actual wound, caused by bacteria colonization, for example (Ehrlich, 1998;Fukai et al, 2005), which is exacerbated in diabetic patients (Lookingbill et al, 1978;Madsen et al, 1996;Robson, 1997;Sibbald et al, 2000;Baltzis et al, 2014;Eming et al, 2014). This permanent inflammatory state results in early degradation of newly forming tissue, creating a neverending loop of wound healing (Rogers et al, 1995;Yager et al, 1996;Kahari and Saarialho-Kere, 1997;Trengove et al, 1999;Liu et al, 2009). Furthermore, this scenario gets even more complex in the presence of bacteria capable of forming biofilms in diabetic foot wounds such as Pseudomonas aeruginosa (Uckay et al, 2015) and multidrug-resistant Staphylococcus aureus (Banu et al, 2015).…”