Pharmacological Intervention And Its Potential Mechanistic Action In Treating The Residue Of Extracranial Arteriovenous Malformation

Objective Arteriovenous Malformation(AVM)is a congenital high-flow vascular malformation caused by the lack of a normal capillary network between the arterial system and the venous system.It is rare but is the most risky and difficult one to cure.Nowadays,the treatment of extracranial AVM mainly focuses on patients with progressive arteriovenous malformation,including surgical resection,endovascular embolization and anhydrous ethanol intervention.However,most interventions cause incomplete ablation of AVM due to the high risk.Residual AVM lesions may give rise to recurrence and deterioration,leaving AVM patients physically and mentally exhausted.Therefore,to eliminate the residual lesions of AVM and limit its recurrence are of extremely important clinical significance.Here we retrospectively analyze the effectiveness of bleomycin in the treatment of residual lesions,and explores its potential mechanistic action of bleomycin,in the hope to pave the way for future therapeutic breakthrough in treating AVM.Methods A retrospective study of patients,from January 2016 to January 2018,who underwent surgical resection or absolute ethanol intervention in our vascular malformation center were selected.Patients who received bleomycin for the treatment of residual arteriovenous malformations were reviewed to demonstrate the efficacy and safety of bleomycin in treating residual lesions.The potential mechanism of action of bleomycin was revealed by pathology and molecular experiments.Results Twenty-one patients with residual arteriovenous malformations treated with bleomycin met the criteria and completed the final evaluation.There are 6 male patients and 15 female patients.The average age of the patients was 25.4 ± 7.6 years.Of the 21 patients,9 had only surgery,9 had only received ethanol intervention,and 3 had both surgery and absolute ethanol.There were 18(85.7%)patients with residual arteriovenous malformations responded well and 7(33.3%)patients achieved complete response and 11(61.1%)patients had partial response.Pathological comparison showed that the neoadjuvant arteries in the lesions after bleomycin treatment were significantly reduced.Further molecular experiments suggested that bleomycin significantly reduced the expression of transcriptome and protein levels of the proangiogenic protein CLEC14 A.Conclusions Bleomycin can effectively and safely treat residual arteriovenous malformations after surgical resection and anhydrous ethanol intervention,and the possible mechanism of action of bleomycin is to reduce the expression of shear-stress sensitive CLEC14 A protein,which inhibits angiogenesis in residual arteriovenous malformations to curb its progression.The mechanism needs to be further explored.