TY  - CONF
A1  - Kashefiolasl, Sepide
A1  - Leisegang, Matthias
A1  - Patel, Rajan
A1  - Kan, Peter
A1  - Förch, Christian
A1  - Du Mesnil de Rochemont, Richard Klaus Frieder
A1  - Seifert, Volker
A1  - Brandes, Ralf
A1  - Prinz, Vincent Matthias
A1  - Konczalla, Jürgen
A1  - Burkhardt, Jan-Karl
A1  - Czabanka, Marcus Alexander
T1  - Propranolol as a potentially novel treatment of arteriovenous malformations: from bench to bedside
T2  - Brain and Spine
N2  - Background: 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;OR13). Patients under β-blocker-treatment showed a significant higher chance for a lower Spetzler-Martin-grade ≤III (p<0,0001;OR6,5) and a lower risk for the presence of an associated aneurysm (p<0,0001;OR3,6).
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,OR0,2).
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.
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/78290
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-782907
SN  - 2772-5294
VL  - 2
IS  - Supplement 2, 101207
PB  - Elsevier
CY  - Amsterdam
ER  -