Common Variants in Interleukin-1-Beta Gene Are Associated with Intracranial Hemorrhage and Susceptibility to Brain Arteriovenous Malformation

Kim, Helen; Hysi, Pirro G.; Pawlikowska, Ludmila; Poon, Annie; Burchard, Esteban G.; Zaroff, Jonathan G.; Sidney, Stephen; Ko, Nerissa; Achrol, Achal S.; Lawton, Michael T.; McCulloch, Charles E.; Kwok, Pui‐Yan; Young, William L.

doi:10.1159/000185609

Cited by 85 publications

(66 citation statements)

References 78 publications

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“…Furthermore, recent evidence suggests that ALK1 is associated with vascular remodeling and arterialization in response to hemodynamic changes, 81 and loss of function of this gene results in loss of distinct arterial and venous boundaries in mice. 83,86 Consistent with increasing evidence implicating inflammation in the pathophysiology of BAVM, [15][16][17]71 recent studies of promoter polymorphisms in inflammatory cytokine genes have included the following: 1) association of promoter polymorphisms in IL-1β with BAVM susceptibility; 50 2) association of a promoter polymorphism in IL-6 with clinical presentation of ICH in BAVM and correlation of IL-6 mRNA and protein levels in resected AVM tissue with genotype;…”

Section: Genetic Considerationsmentioning

confidence: 93%

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

Achrol¹,

Guzman²,

Varga³

et al. 2009

FOC

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Brain arteriovenous malformations (BAVMs) are an important cause of intracerebral hemorrhage (ICH) in young adults. Biological predictors of future ICH risk are lacking, and controversy exists over previous studies of natural history risk among predominantly ruptured BAVM cohorts. Recent studies have suggested that the majority of BAVMs are now diagnosed as unruptured lesions, and that the risk according to natural history among these lesions may be less than previously assumed. In the first part of this review, the authors discuss available data on the natural history of BAVMs and highlight the need for future studies that aim to develop surrogate biomarkers of disease progression that accurately predict future risk of ICH in BAVMs. The etiology of BAVM remains unknown. Recent studies have suggested a role for genetic factors in the pathogenesis of sporadic BAVM, which is further supported by reports of familial occurrence of BAVM and association with known systemic genetic disorders (such as Osler-Weber-Rendu disease, Sturge-Weber disease, and Wyburn-Mason syndrome). Molecular characterization of BAVM tissue demonstrates a highly angiogenic milieu with evidence of increased endothelial cell turnover. Taken together with a number of reports of de novo BAVM formation, radiographic growth after initial BAVM diagnosis, and regrowth after successful treatment of BAVM, these findings challenge the long-held assumption that BAVMs are static lesions of congenital origin. In the second part of this review, the authors discuss available data on the origins of BAVM and offer insights into future investigations into genetics and endothelial progenitor cell involvement in the pathogenesis of BAVM. Current treatment options for BAVM focus on removal or obliteration of the lesion in an attempt to protect against future ICH risk, including microsurgical resection, endovascular embolization, and stereotactic radiosurgery (SRS). In the third part of this review, the authors discuss available data on SRS in BAVMs and highlight the need for future studies on the radiobiology of BAVMs, especially in regard to biomarker detection for tracking SRS response during the latency period. Insights from future investigations in BAVM may not only prove important for the development of novel therapies and relevant biomarkers for BAVM, but could also potentially benefit a variety of other disorders involving new vessel formation in the CNS, including stroke, tumors, moyamoya disease, and other cerebrovascular malformations.

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Section: Genetic Considerationsmentioning

confidence: 93%

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

Achrol¹,

Guzman²,

Varga³

et al. 2009

FOC

Self Cite

View full text Add to dashboard Cite

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“…Inhibition of the neuronal NLRP1 inflammasome (which is involved in the processing and release of IL-1 through the activation of caspase-1) improves outcome after stroke, traumatic or spinal cord injury [19,20,21]. Further support for a role for IL-1 in stroke comes from the observations that IL-1 or IL-1Ra gene polymorphisms are associated with altered susceptibility to stroke, carotid atherosclerosis and intracranial haemorrhage in humans [22,23,24,25,26,27]. …”

Section: Il-1 and Acute Brain Injurymentioning

confidence: 99%

Interleukin-1 and Stroke: Biomarker, Harbinger of Damage, and Therapeutic Target

Pinteaux¹,

Rothwell²,

Allan³

2011

Cerebrovasc Dis

105

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Inflammation is established as a contributor to cerebrovascular disease. Risk factors for stroke include many conditions associated with chronic or acute inflammation, and inflammatory changes in the brain after cerebrovascular events contribute to outcome in experimental studies, with growing evidence from clinical research. The brain is extremely susceptible to inflammatory challenge, but resident glia, endothelial cells and neurones can all mount a pronounced inflammatory response to infection or injury. Recent discoveries highlight the importance of peripherally-derived immune cells and inflammatory molecules in various central nervous system disorders, including stroke. The inflammatory cytokine, interleukin-1 (IL-1), plays a pivotal role in both local and systemic inflammation, and is a key driver of peripheral and central immune responses to infection or injury. Inhibition of IL-1 has beneficial effects in a variety of experimental paradigms of acute brain injury and is a promising clinical target in stroke. We propose that blockade of IL-1 could be therapeutically useful in several diseases which are risk factors for stroke, and there is already considerable pre-clinical and clinical evidence that inhibition of IL-1 by IL-1 receptor antagonist may be valuable in the management of acute stroke.

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“…In humans, polymorphisms in the IL-1␤ promoter are associated with increased risk of hemorrhage in brain arteriovenous malformation patients; elevated IL-1␤ levels are reported in induced sputum, bronchoalveolar lavage, and serum from COPD patients (17)(18)(19). Serum IL-1␤ levels correlate with physiologic and clinical measures of COPD severity (19).…”

mentioning

confidence: 99%

Interleukin-1β Induces Increased Transcriptional Activation of the Transforming Growth Factor-β-activating Integrin Subunit β8 through Altering Chromatin Architecture

Markovics

Araya

Cambier

et al. 2011

Journal of Biological Chemistry

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Background: IL-1␤ acts on fibroblasts inducing TGF-␤-dependent profibrogenic responses. Results: IL-1␤ increases expression of the TGF-␤-activating integrin ␤8 subunit through altering nucleosomal positioning at the ITGB8 promoter. Conclusion: IL-1␤ increases accessibility of transcription factors to the ITGB8 promoter in lung fibroblasts through chromatin remodeling.Significance: This provides evidence for chromatin architectural changes mediating IL-1␤ profibrotic programs.

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Common Variants in Interleukin-1-Beta Gene Are Associated with Intracranial Hemorrhage and Susceptibility to Brain Arteriovenous Malformation

Cited by 85 publications

References 78 publications

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

Pathogenesis and radiobiology of brain arteriovenous malformations: implications for risk stratification in natural history and posttreatment course

Interleukin-1 and Stroke: Biomarker, Harbinger of Damage, and Therapeutic Target

Interleukin-1β Induces Increased Transcriptional Activation of the Transforming Growth Factor-β-activating Integrin Subunit β8 through Altering Chromatin Architecture

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