Der molekulare Bypass: eine etablierte Methode zur Revaskularisation von inoperablen pAVK-Patienten oder nur eine Zukunftsvision?^[*]

Zusammenfassung

Das Kollateralenwachstum ist ein physiologischer Prozess, der nicht bei jedem Menschen gleichermaßen ausgeprägt wird. Kommt es in einem Gefäßsystem zu einer hämodynamisch relevanten Stenose, wird der Blutfluss durch Umgehungskreisläufe geleitet, um minderdurchblutetes Gewebe zu versorgen. Diese Umgehungskreisläufe existieren bereits auf kapillarer Ebene und sind per definitionem keine echten neuen Gefäße. Postnatale Vaskulogenese (wahre Gefäßneubildung) kommt beim adulten Organismus lediglich bei der Tumorvaskularisation, der Wundheilung, im Endometrium und im Rahmen chronischer Erkrankungen wie der rheumatoiden Arthritis und der Psoriasis vor. Da Gefäßstenosen, Gefäßverschlüsse und Verschlüsse das kardiovaskuläre Krankheitsbild bestimmen, sind deren Wiedereröffnung oder die Anlage von künstlichen Bypässen effektive Therapieansätze. Jedoch sind die vorhandenen Strategien bei vielen Patienten bereits ausgeschöpft, sodass die Förderung des natürlichen Kollateralenwachstums, die Arteriogenese, ein neues Feld therapeutischer Optionen eröffnet. Monozyten spielen hier eine Schlüsselrolle, da sie an Orten der Arteriogenese anzutreffen sind und dort multiple Wachstumsfaktoren, die für die Kollateralenentstehung notwendig sind, sezernieren. Ebenso werden Stammzellen unterschiedlicher Herkunft, endotheliale Vorläuferzellen (Progenitorzellen) oder mononukleäre Zellen derzeit zur Förderung des Gefäßwachstums eingesetzt. Auch die Applikation von Wachstumsfaktoren wie VEGF, MCP-1, GM-CSF sind hier bereits in klinischen Studien angewandt worden. Dieser Übersichtsartikel erläutert die Physiologie und Pathophysiologie von Gefäßstenosen und deren Kompensationsmechanismen und fasst bisherige Therapieansätze und neue Strategien für inoperable pAVK-Patienten zusammen. Die aktuelle Studienlage zur zellbasierten Therapie des molekularen Bypasses sowie die Ergebnisse bisheriger Techniken wie die der PTA, Stentimplantationen und der Bypassanlagen werden übersichtlich dargestellt.

Abstract

Collateral vessel growth is a physiological process that is not equally pronounced in all people. After the development of a haemodynamically relevant stenosis in vascular systems, blood flow is directed through a collateral circulation to supply ischaemic tissue. This collateral circulation exists on the capillary level and by definition, is not composed of real new vessels. Postnatal vasculogenesis (true neovascularisation) occurs in the adult organism in tumour vascularisation, wound healing, in the endometrium, and in the context of chronic diseases such as rheumatoid arthritis and psoriasis. Reopening of the occluded vessel or use of artificial bypass grafts are the most attractive therapeutic approaches for treating peripheral arterial and coronary artery disease. These strategies have been exhausted in many patients; therefore augmentation of arteriogenesis can be more useful. Arteriogenesis, the promotion of natural collateral growth, is a hot topic in vascular research. Monocytes play a key role in arteriogenesis by “homing” to areas of collateral vessel growth and locally secrete multiple essential growth factors. Furthermore, stem cells of different origins, endothelial progenitor cells or mononuclear cells are currently being used to promote vessel growth. Also, the application of growth factors such as VEGF, MCP-1, GM-CSF have been already used in clinical trials. This review article describes the physiology and pathophysiology of vascular stenoses and their compensation mechanisms. The review also gives an overview of current treatment approaches and new strategies for non-operable PAD patients. The article presents the current cell and growth factor-related studies, as well as results of balloon dilatation and stent implantation or bypass surgery studies for improvement of revascularisation.

Schlüsselwörter

Kollateralenwachstum - Arteriogenese - Monozyt - pAVK - Ischämie

Key words

collateral vessel growth - arteriogenesis - monocyte - PAD - ischaemia

^* Prof. Dr. Dr. H. Lippert gewidmet

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