A Biological Approach to Treating Brain Arteriovenous Malformations

Zammar, Samer G.; Tecle, Najib E. El; Ahmadieh, Tarek Y. El; McClendon, Jamal; Comair, Youssef G.; Bendok, Bernard R.

doi:10.1227/01.neu.0000445336.35080.60

Cited by 14 publications

(16 citation statements)

References 4 publications

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“…Brain endothelial cells (BECs) of BAVMs are considered strikingly active, proliferate and migrate faster than normal endothelial cells, and exhibit atypical functions aside from modified expression levels of growth factors modulating angiogenesis [9,22,52]. Increased levels of thrombospondin-1 (TSP-1), an antagonist of Vascular Endothelial Growth Factor A (VEGF-A) have been discerned within BAVM BECs, as a result of the high levels of "inhibitor of DNA-binding protein A" (Id-1), which represses the transcription of TSP-1 [19,20,53].…”

Section: Mir-18amentioning

confidence: 99%

“…MicroRNAs (miRNA or miR) represent short strands of non-coding ribonucleic acid (RNA), approximately 20-22 nucleotides long, with the capacity to regulate the expression of target genes via the complete or partial binding onto their respective complementary sequences [17][18][19][20][21][22]. As a result, they hamper translation while also stimulating mRNA degradation.…”

Section: Introductionmentioning

confidence: 99%

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An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Florian

Buruiană

Şuşman

et al. 2021

Cells

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Background: Brain arteriovenous malformations (BAVMs) and cerebral cavernous malformations (CCMs) are rare developmental anomalies of the intracranial vasculature, with an irregular tendency to rupture, and as of yet incompletely deciphered pathophysiology. Because of their variety in location, morphology, and size, as well as unpredictable natural history, they represent a management challenge. MicroRNAs (miRNAs) are strands of non-coding RNA of around 20 nucleotides that are able to modulate the expression of target genes by binding completely or partially to their respective complementary sequences. Recent breakthroughs have been made on elucidating their contribution to BAVM and CCM occurrence, growth, and evolution; however, there are still countless gaps in our understanding of the mechanisms involved. Methods: We have searched the Medline (PubMed; PubMed Central) database for pertinent articles on miRNAs and their putative implications in BAVMs and CCMs. To this purpose, we employed various permutations of the terms and idioms: ‘arteriovenous malformation’, ‘AVM’, and ‘BAVM’, or ‘cavernous malformation’, ‘cavernoma’, and ‘cavernous angioma’ on the one hand; and ‘microRNA’, ‘miRNA’, and ‘miR’ on the other. Using cross-reference search; we then investigated additional articles concerning the individual miRNAs identified in other cerebral diseases. Results: Seven miRNAs were discovered to play a role in BAVMs, three of which were downregulated (miR-18a, miR-137, and miR-195*) and four upregulated (miR-7-5p, miR-199a-5p, miR-200b-3p, and let-7b-3p). Similarly, eight miRNAs were identified in CCM in humans and experimental animal models, two being upregulated (miR-27a and mmu-miR-3472a), and six downregulated (miR-125a, miR-361-5p, miR-370-3p, miR-181a-2-3p, miR-95-3p, and let-7b-3p). Conclusions: The following literature review endeavored to address the recent discoveries related to the various implications of miRNAs in the formation and growth of BAVMs and CCMs. Additionally, by presenting other cerebral pathologies correlated with these miRNAs, it aimed to emphasize the potential directions of upcoming research and biological therapies.

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Section: Mir-18amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Florian

Buruiană

Şuşman

et al. 2021

Cells

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“…Moreover, miR-18a successfully penetrates target cells without additional reagents, allowing for intravenous or endovascular infusion, making it a promising therapeutic option. 11,58 The effect of radiation on the molecular process of AVM pathophysiology is of particular interest given its known ability, delivered as SRS, to drive endothelial proliferation and ultimately AVM obliteration. 43 Radiation elevates proapoptotic factors, such as p53, p21Waf-1, and mdm-2 mRNA.…”

Section: 58mentioning

confidence: 99%

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Rangel-Castilla¹,

Russin²,

Martinez-del-Campo³

et al. 2014

FOC

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Object Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. Methods A PubMed search was performed using the key words “genetic,” “molecular,” “brain,” “cerebral,” “arteriovenous,” “malformation,” “rupture,” “management,” “embolization,” and “radiosurgery.” Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Results Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Conclusions Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

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“…21 Thus, an infusion of the miR-18a by endovascular catheters could theoretically rectify the functionally anomalous AVM-BECs. 22…”

Section: Ncrnas Associated With Sporadic Bavmsmentioning

confidence: 99%

Molecular Biomarkers and Drug Targets in Brain Arteriovenous and Cavernous Malformations: Where Are We?

Venugopal

Sumi

2022

Stroke

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Vascular malformations of the brain (VMB) comprise abnormal development of blood vessels. A small fraction of VMBs causes hemorrhages with neurological morbidity and risk of mortality in patients. Most often, they are symptomatically silent and are detected at advanced stages of disease progression. The most common forms of VMBs are arteriovenous and cavernous malformations in the brain. Radiopathological features of these diseases are complex with high phenotypic variability. Early detection of these malformations followed by preclusion of severe neurological deficits such as hemorrhage and stroke is crucial in the clinical management of patients with VMBs. The technological advances in high-throughput omics platforms have currently infused a zest in translational research in VMBs. Besides finding novel biomarkers and therapeutic targets, these studies have withal contributed significantly to the understanding of the etiopathogenesis of VMBs. Here we discuss the recent advances in predictive and prognostic biomarker research in sporadic and familial arteriovenous malformations as well as cerebral cavernous malformations. Furthermore, we analyze the clinical applicability of protein and noncoding RNA-based molecular-targeted therapies which may have a potentially key role in disease management.

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A Biological Approach to Treating Brain Arteriovenous Malformations

Cited by 14 publications

References 4 publications

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

Molecular Biomarkers and Drug Targets in Brain Arteriovenous and Cavernous Malformations: Where Are We?

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