Lässt sich die Expression von EZM-Proteinen durch Kompression beeinflussen?

Zusammenfassung

Hintergrund: In den fortgeschrittenen Stadien der chronischen venösen Insuffizienz (CVI) werden die Proteine Tenascin C, Fibrillin 2 und α-smooth muscle Actin (αSMA) vermehrt ex-primiert. Diese Proteine der Extrazellularmatrix werden im Rahmen der Wundheilung und in hypertrophen Narben verstärkt gebildet. Die pathologische Expression in hypertrophen Narben kann durch Kompression normalisiert werden.

Fragestellung: Wird die Expression der Proteine Tenascin C, Fibrillin 2 und αSMA im Stadium C2 und C4 der CVI durch Kompression be-einflusst?

Methode: Untersucht wurden 23 Patienten mit CVI (12 Stadium C2, 11 Stadium C4) ohne bisherige Kompressionstherapie. Sie erhielten für 2 bzw. 4 Wochen einen medizinischen Kompressionsstrumpf (Klasse II oder Klasse III). An Tag 1, 14 und 28 wurde jeweils eine Hautprobe am Innenknöchel entnommen.

Ergebnisse: Im Stadium C2 liegt ein Expressionsmuster wie in normaler Haut vor. Im Stadium C4 variiert die Expression je nach kli-nischem Erscheinungsbild. Bei Dermatoliposklerose zeigt sich in der gesamten Dermis eine vermehrte Expression von Fibrillin 2 und Tenascin C. Bei Hyperpigmentierung oder Stauungsekzem zeigt sich in wenigen Fällen eine vermehrte Expression in der Tiefe bzw. entlang der Basalmembran. αSMA lässt sich nur in den Wänden der dermalen Gefäße darstellen. Die Kompressionstherapie bewirkt in dem Untersuchungszeitraum keine Änderung der Protein-expression.

Schlussfolgerung: Fibrillin 2 und Tenascin C zei-gen sich erst im Falle einer bestehenden Sklerose. Ein potenzieller Einfluss von Kompression auf die Expression dieser Parameter muss in weiteren Studien untersucht werden.

Summary

Background: The advanced states of the chronic venous insufficiency (CVI) are char-acterized by an increased protein expression of tenascin C, fibrillin 2 and α-smooth muscle actin. These proteins of the extracellular matrix are augmentedly expressed during wound healing in hypertrophy scars.

Objective: Is the expression of the proteins tenascin C, fibrillin2 und α-smooth muscle actin suggestible by compression?

Patient and Methods: We investigated the skin of 23 patients (12 in state C2 and 11 in state C4). These patients were not treated with compression therapy before. They got compression stockings for 2 or 4 weeks (VenoTrain delight or VenoTrain micro). On day 1, 14 and 28 we took a skin sample from the ankle.

Results: In stadium C2 of the CVI there was an expression as in normal skin, a small band belong the dermal-epidermal junction and in blood vessels. In stadium C4 the expression varied corresponding to the clinical figure. In lipodermatosclerosis, tenascin C and fibrillin 2 were increasingly expressed in the whole dermis. On hyperpigmentation or in stasis dermatitis there was an increased expression just in a few biopsies. In some cases the augmented expression was present in the deeper dermis, in other cases in the dermal-epidermal junction.α-smooth muscle actin was expressed in both stadium C2 and C4 only in blood vessels. Druing the study an effect of compression therapy on protein expression was not obvious.

Conclusion: Tenascin C and fibrillin 2 were only expressed in the state of a sclerosis. The influence of compression on the expression of extracellular matrix proteins needs further investigations.

Schlüsselwörter

CVI - Tenascin C - Fibrillin 2 - α-smooth muscle actin

Keywords

CVI - Tenascin C - Fibrillin 2 - α-smooth muscle actin

• Literatur

• 1 Kistner RL, Eklöf B, Masuda EM. Diagnosis of chronic venous diseases of the lower extremities: the „CEAP“ classification. Mayo Clin Proc 1996; 71: 338-345.
• 2 Rabe E, Gerlach HE. Praktische Phlebologie Empfehlungen zur differenzierten Diagnostik und Therapie phlebologischer Krankheitsbilder. 2. Auflage. Stuttgart: Georg Thieme Verlag; 2006
• 3 Rabe E, Pannier-Fischer F, Bromen K. et al. Bonn Vein Study by the German Society of Phlebology: Epidemiological study to investigate the prevalence and severity of chronic venous disorders in the urban and rural residential populations. Phlebologie 2003; 32 (01) 1-14.
• 4 Gallenkemper G, Bulling B, Gerlach H. et al. Guidelines in diagnosis and therapy of chronic venous insufficiency. Phlebologie 2000; 29 (04) 102-105.
• 5 Gschwandtner ME, Ehringer H. Microcirculation in chronic venous insufficiency. Vascular Medicine 2001; 6 (03) 169-179.
• 6 Burnand KG, Whimster I, Naidoo A, Browse NL. Pericapillary fibrin in the ulcer-bearing skin of the leg: The cause of lipodermatosclerosis and venous ulceration. British Medical Journal 1982; 285 6348 1071-1072.
• 7 Veraart J, Verhaegh M, Neumann HAM. et al. Adhesion molecule expression in venous leg ulcers. Vasa 1993; 22: 213-219.
• 8 Herrick SE, Sloan P, McGurk M. et al. Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. American Journal of Pathology 1992; 141 (05) 1085-1095.
• 9 Coleridge Smith PD, Thomas P, Scurr JH, Dormandy JA. Causes of venous ulceration: A new hypothesis. British Medical Journal 1988; 296 6638 1726-1727.
• 10 Brinckmann J, Hunzelmann N, Kahle B. et al. Enhanced fibrillin-2 expression is a general feature of wound healing and sclerosis: Potential alteration of cell attachment and storage of TGF-α. Laboratory Investigation 2010; 90 (05) 739-752.
• 11 Brinckmann J, Neess CM, Gaber Y. et al. Different pattern of collagen cross-links in two sclerotic skin diseases: Lipodermatosclerosis and circumscribed scleroderma. Journal of Investigative Dermatology 2001; 117 (02) 269-273.
• 12 Hinz B. The myofibroblast: Paradigm for a mechanically active cell. Journal of Biomechanics 2010; 43 (01) 146-155.
• 13 Hinz B. Formation and function of the myofibroblast during tissue repair. Journal of Investigative Dermatology 2007; 127 (03) 526-537.
• 14 Welt K, Gall N, Sindrilaru A, Scharffetter-Kochanek K. Pathogenesis of the chronic ulcus cruris venosum. Phlebologie 2005; 34 (02) 81-86.
• 15 Hinz B, Phan SH, Thannickal VJ. et al. The myofibroblast: One function, multiple origins. American Journal of Pathology 2007; 170 (06) 1807-1816.
• 16 Costa AMA, Peyrol S, Pôrto LC. et al. Mechanical forces induce scar remodeling: Study in non-pressuretreated versus pressure-treated hypertrophic scars. American Journal of Pathology 1999; 155 (05) 1671-1679.
• 17 Spilker G, Tolksdorf-Kremmer A, Küppers S. Kom pressionstherapie. In: Handbuch der Verbrennungstherapie. Bruck JC, Müller FE, Steen M. (eds) Landsberg: ecomed Verlagsgesellschaft; 2002: 353-365.
• 18 Lightner VA, Gumkowski F, Bigner DD, Erickson HP. Tenascin/hexabrachion in human skin: Biochemical identification and localization by light and electron microscopy. Journal of Cell Biology 1989; 108 (06) 2483-2493.
• 19 Eklöf B, Rutherford RB, Bergan JJ. et al. Revision of the CEAP classification for chronic venous disorders. J Vasc Surg 2004; 40 (06) 1248-1252.