Chapter title |
Genetic considerations relevant to intracranial hemorrhage and brain arteriovenous malformations.
|
---|---|
Chapter number | 38 |
Book title |
Cerebral Hemorrhage
|
Published in |
Acta neurochirurgica Supplement, January 2008
|
DOI | 10.1007/978-3-211-09469-3_38 |
Pubmed ID | |
Book ISBNs |
978-3-21-109468-6, 978-3-21-109469-3
|
Authors |
Kim, H, Marchuk, D A, Pawlikowska, L, Chen, Y, Su, H, Yang, G Y, Young, W L, H. Kim, D. A. Marchuk, L. Pawlikowska, Y. Chen, H. Su, G. Y. Yang, W. L. Young, Kim, H., Marchuk, D. A., Pawlikowska, L., Chen, Y., Su, H., Yang, G. Y., Young, W. L. |
Abstract |
Brain arteriovenous malformations (AVMs) cause intracranial hemorrhage (ICH), especially in young adults. Molecular characterization of lesional tissue provides evidence for involvement of both angiogenic and inflammatory pathways, but the pathogenesis remains obscure and medical therapy is lacking. Abnormal expression patterns have been observed for proteins related to angiogenesis (e.g., vascular endothelial growth factor, angiopoietin-2, matrix metalloproteinase-9), and inflammation (e.g., interleukin-6 [IL-6] and myeloperoxidase). Macrophage and neutrophil invasion have also been observed in the absence of prior ICH. Candidate gene association studies have identified a number of germline variants associated with clinical ICH course and AVM susceptibility. A single nucleotide polymorphism (SNP) in activin receptor-like kinase-1 (ALK-1) is associated with AVM susceptibility, and SNPs in IL-6, tumor necrosis factor-alpha (TNF-alpha), and apolipoprotein-E (APOE) are associated with AVM rupture. These observations suggest that even without a complete understanding of the determinants of AVM development, the recent discoveries of downstream derangements in vascular function and integrity may offer potential targets for therapy development. Further, biomarkers can now be established for assessing ICH risk. These data will generate hypotheses that can be tested mechanistically in model systems, including surrogate phenotypes, such as vascular dysplasia and/or models recapitulating the clinical syndrome of recurrent spontaneous ICH. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Finland | 1 | 2% |
Canada | 1 | 2% |
Brazil | 1 | 2% |
Unknown | 46 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Doctoral Student | 8 | 16% |
Student > Ph. D. Student | 7 | 14% |
Researcher | 7 | 14% |
Student > Bachelor | 6 | 12% |
Other | 4 | 8% |
Other | 12 | 24% |
Unknown | 5 | 10% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 21 | 43% |
Agricultural and Biological Sciences | 12 | 24% |
Neuroscience | 6 | 12% |
Biochemistry, Genetics and Molecular Biology | 2 | 4% |
Unknown | 8 | 16% |