Mechanismen und Möglichkeiten einer therapeutischen Stimulation der Arteriogenese

Zusammenfassung

Die Stimulation des Kollateralarterienwachstums (Arteriogenese) ist eine vielversprechende Alternative zur nichtinvasiven Behandlung stenosierender arterieller Gefäßkrankheiten wie der koronaren Herzkrankheit, der peripheren oder zerebralen arteriellen Verschlusskrankheit. Patienten, die einem klassischen Revaskularisationsverfahren nicht mehr erfolgreich zugeführt werden können, könnten von der Stimulation der adaptiven Arteriogenese profitieren. Die zu Grunde liegenden Mechanismen sind experimentell gut belegt. Hierzu gehören eine Erhöhung der Scherkraft bei Stenose einer größeren Arterie, Adhäsion, Transmigration und perivaskuläre Akkumulation von Monozyten um die kollateralarterielle Arteriole, Wachstumsfaktorsezernierung und Proliferation von Endothel- und glatten Gefäßmuskelzellen. Die therapeutische Stimulation der Arteriogenese durch Zytokine gelingt im experimentellen Modell bereits sehr gut. An der Umsetzung der Erkenntnisse in die klinische Praxis muss noch gearbeitet werden. Problematisch sind die biologisch-anatomischen Unterschiede zwischen dem gesundem Versuchstier und dem oft multimorbiden Patienten, mögliche schädliche Wirkungen einer pro-arteriogenen Therapie sowie die Verwendung geeigneter klinischer Endpunkte zur exakten Quantifizierung des Kollateralarterienwachstums. Erste Untersuchungen der humanen Arteriogenese zeigen große interindividuelle Unterschiede und weisen auf eine Bedeutung anti-arteriogener Mechanismen bei Patienten mit hohem kardiovaskulärem Risiko.

Summary

The stimulation of collateral artery growth (arteriogenesis) is a promising alternative approach to non-invasively treat arterial obstructive disease, such as coronary, peripheral or cerebral artery disease. Patients unable to undergo conventional revascularization strategies may benefit from adaptive arteriogenesis. Underlying mechanisms are experimentally validated and include an increase in shear stress after obstruction or occlusion of a major artery; monocyte adhesion, transmigration and perivascular accumulation, secretion of growth factors; and smooth muscle and endothelial cell proliferation and growth of pre-existent collateral arteries. Therapeutic stimulation of arteriogenesis with cytokines has been successfully performed in experimental models. Translation into clinical practice, however, has hitherto been problematic. Reasons for this include differences between the healthy laboratory animal and an often severely diseased patient, possible harmful effects of pro-arteriogenic therapies and unsuitable clinical endpoints for the detection of collateral artery growth. Recent investigations of human arteriogenesis demonstrate significant inter-individual differences and point towards the importance of anti-arteriogenic mechanisms in patients with impaired adaptive arteriogenesis and high cardiovascular risk factors.

Schlüsselwörter

Arteriogenese - Kollateralarterienwachstum - Angiogenese - Monozyten - Koronare Herzkrankheit - Atherosklerose

Keywords

arteriogenesis - collateral artery growth - monocytes - coronary artery disease - vascular biology - cytokines

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