Artikel
Propranolol as a potentially novel treatment of arteriovenous malformations – from bench to bedside
Propanolol als mögliche Behandlung für arteriovenöse Malformationen: Aus dem Forschungslabor ans Krankenbett
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Autoren
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Sepide Kashefiolasl
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
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Matthias Leisegang
- Universitätsklinikum Frankfurt, Kardiovaskuläre Physiologie, Frankfurt a. M., Deutschland
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Sven König
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
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Rajan Patel
- Baylor College of Medicine, Department of Neurosurgery, Houston, TX, Vereinigte Staaten
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Peter Kan
- Baylor College of Medicine, Department of Neurosurgery, Houston, TX, Vereinigte Staaten
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Christian Foerch
- Universitätsklinikum Frankfurt, Neurologie, Frankfurt a. M., Deutschland
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Richard Du Mesnil
- Universitätsklinikum Frankfurt, Neuroradiologie, Frankfurt a. M., Deutschland
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Volker Seifert
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
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Ralf Brandes
- Universitätsklinikum Frankfurt, Kardiovaskuläre Physiologie, Frankfurt a. M., Deutschland
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Vincent Prinz
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
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Marcus Czabanka
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
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Jan-Karl Burkhardt
- Baylor College of Medicine, Department of Neurosurgery, Houston, TX, Vereinigte Staaten
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Jürgen Konczalla
- Universitätsklinikum Frankfurt, Klinik für Neurochirurgie, Frankfurt a. M., Deutschland
| Veröffentlicht: | 25. Mai 2022 |
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Gliederung
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Objective: Propranolol is a non-selective blocker of the β-adrenergic receptor and has been used for treatment of proliferative infantile hemangiomas. The vasoconstrictive and antiangiogenic effects of propranolol led us to explore its potential application for the treatment of AVMs.
Methods: AVM tissue was cultured after surgical resection in the presence of 100μM propranolol or solvent DMSO. After incubation for 72 hours, tissue was harvested for testing. The expression levels of SDF1α, CXCR4, VEGF and HIF-1 was measured by rt-PCR. Furthermore, data of patients in 2 vascular centres harboring AVM was retrospectively interrogated for a time period of 20 years. The database included information about hemorrhage, AVM size and antihypertensive medication. Descriptive analyses were performed, focusing on the risk of hemorrhage, size of the lesion at presentation and clinical follow-up in patients on β-blocker medication versus those who were not.
Results: Among 483 patients, 73 (15%) were under β-blocker treatment. 48% AVMs presented with hemorrhage at diagnosis. Patients under β-blocker treatment had a lower risk of hemorrhage at the time of diagnosis in a univariate analysis (p<0,0001; OR 13). Patients under β-blocker treatment showed a significant higher chance for a lower Spetzler-Martin grade ≤III (p<0,0001; OR 6,5) and a lower risk for the presence of an associated aneurysm (p<0,0001; OR 3,6). Multivariate analysis including Spetzler-Martin Grading, young age ≤ 50, presence of associated aneurysm and β-blocker treatment showed reduced risk for hemorrhage under β-blocker treatment (p<0,01, OR 0,2). The expression of CXCR4 was suppressed by propranolol most likely through the HIF-1 pathways. The gene expression of vasculogenesis factors was decreased in with propranolol incubated AVMs.
Conclusion: β-Blocker medication seems to be associated with a decreased risk of AVM-related hemorrhage and AVM-size at presentation or during follow-up. Propranolol inhibits SDF1α-induced vasculogenesis by suppressing the expression of CXCR4 most likely through the HIF-1 pathways. Therefore, SDF1α/CXCR4 axis plays an important role in the vasculogenesis and migration of inflammatory cells in AVM lesions.
