Zusammenfassung
Degenerative Veränderungen der Achillessehne entstehen bevorzugt in Regionen, in denen das Sehnengewebe hypo- oder avaskulär ist (Insertion, Sehnentaille). Die vaskulären Proliferationen in degenerativ geschädigtem Sehnengewebe ist das Ergebnis der HIF-1-vermittelten Expression des Angiogenesefaktors VEGF. Die VEGF-Expression lässt sich durch mechanischen Stress, Hypoxie und inflammatorische Zytokine stimulieren. Alle 3 Faktoren sind äthiologisch für die Entstehung degenerativer Sehnenerkrankungen bedeutsam.
Die Neoangiogenese spielt im Rahmen der Pathogenese degenerativer Sehnenerkrankungen eine wichtige Rolle. Einerseits wachsen mit den Blutgefäßen Nervenendigungen in das Sehnengewebe ein, die wesentlich für das Hauptsymptom Schmerz verantwortlich sind. Andererseits wird die mechanische Festigkeit des Sehnengewebes durch das Einwachsen der Blutgefäße reduziert. Auf diese Weise wird die Entstehung spontaner Sehnenrupturen begünstigt. Bei dem Prozess der „angiogenetischen Gewebsdestruktion“ spielt neben der direkten Schädigung durch das „Einwachsen“ auch die VEGF-induzierte Expression von Matrixmetalloproteinasen (MMP) eine Rolle.
Untersuchungen unter Verwendung von Dopplerultraschall (US) haben zeigen können, dass sich die Gefäßneubildungen unter einem exzentrischen Training zurückbilden können. Parallel kommt es zu einer deutlichen Besserung der Schmerzsymptomatik. Bei Patienten, bei denen eine Rückbildung der Gefäßneubildungen ausblieb, blieben die Schmerzen bestehen. Ein weiterer erfolgversprechender Ansatz ist die ultraschallgestützte Sklerosierung der Blutgefäße.
Abstract
In the Achilles tendon, degenerative changes mostly occur in regions that are hypo- or avascular. Angiogenesis is mediated by angiogenic factors and recent studies have shown that vascular endothelial growth factor (VEGF) is highly expressed in degenerative Achilles tendons, whereas VEGF expression is nearly completely downregulated in healthy tendons. VEGF expression in tendon fibroblasts is regulated by the transcription factor hypoxia inducible factor 1 (HIF-1). Several factors are able to upregulate VEGF expression in tenocytes: hypoxia, inflammatory cytokines and mechanical load. Angiogenesis plays an important role in the tendinotic process.
The neovessels are accompanied by small glutamate positive neural structures. This finding suggests that angiogenesis plays an important role in the pain experienced during the degenerative tendon disease. On the other hand, there is some evidence that HIF-1/VEGF induced angiogenesis has an effect on the material properties of the tendinotic tendon tissue. Since VEGF has the potential to stimulate the expression of matrix metalloproteinases and inhibits the expression of tissue inhibitors of matrix metalloproteinases (TIMP) in various cell types this cytokine might play a significant role in the pathogenetic processes during degenerative tendon disease.
These experimental findings are in accordance with clinical results which show that eccentric training leads to a regression of neovessels and decrease of pain. Another strategy is the local administration of a sclerosing agent (Polidocanol) to destroy neovessles. Preliminary results show that both strategies are effective in reducing vascular density and pain.
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Die Arbeiten wurden durch die Deutsche Forschungsgemeinschaft unterstützt (DFG Pu 214/3–1 und Pe 873/2–1). Wir danken Frau Inka Kronenbitter, Herrn Frank Lichte, Frau Marion Lorenzen, Frau Miriam Lemmer, Frau Sonja Seiter, Frau Karin Stengel und Frau Regine Worm für die technische Hilfe.
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Petersen, W., Pufe, T., Pfrommer, S. et al. Überlastungsschäden der Achillessehne: Die Bedeutung von Blutgefäßversorgung und Angiogenese. Orthopäde 34, 533–542 (2005). https://doi.org/10.1007/s00132-005-0808-7
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DOI: https://doi.org/10.1007/s00132-005-0808-7