[Mechanisms influencing cellular physiology as a concept of treatment for wound healing disturbances].
OBJECTIVE
Recent knowledge about repair mechanisms in different types of tissue is the basic of actual therapeutic efforts. Center of several experimental and clinical approaches is the influencing of angiogenesis with an also distinct meaning concerning wound healing. Therefore, application of growth factors, gene transfer, and employment of genetically manipulated cells often aim at angiogenesis. Nevertheless, manipulation of angiogenesis also leads to secondary problems such as hyperpermeability followed by impairment of local wound milieu. Our study was done to identify mechanisms to protect from disturbances of endothelial barrier function.


METHODS
In a first experimental investigation on cultured endothelial cells, the influence of plasma-transglutaminase (Factor XIII) to endothelial barrier function was studied. In a second step, the influence of Factor XIII on wound healing properties was investigated in patients with a chronic venous ulceration.


RESULTS
Activated Factor XIII (FXIIIA*) led to a dose-dependent reduction of endothelial cell permeability of 30 % compared to control with a maximum effect using 1 to 5 U/mL. Clinical investigation revealed a nearly complete reduction of wound secretion.


CONCLUSIONS
Experimental studies revealed that activated Factor XIII stabilizes endothelial barrier under basic conditions as well as under conditions of induced hyperpermeability. Clinical study revealed that Factor XIII also distinctly reduces wound secretion. Therefore, plasma-transglutaminase may offer a new therapeutic option to treat the local or generalized leakage-syndrome.
Wozniak
G
G
Klinik für Gefässchirurgie mit assoziiertem Wundfachzentrum, Knappschaftskrankenhaus, Osterfeldstrasse 157, 46242 Bottrop, Germany. gernold.wozniak@kk-bottrop.de
Noll
T
T
D000287:Administration, Topical; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017719:Diabetic Foot / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D026122:Factor XIIIa / Q000008:administration & dosage*; D005341:Fibrinolysin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014647:Varicose Ulcer / Q000188:drug therapy* / Q000503:physiopathology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D026122:Factor XIIIa; D005341:Fibrinolysin