Abstract
Abstract
Background
Cerebral cavernous malformations (CCMs), a major neurosurgical condition, characterized by abnormally dilated intracranial capillaries, result in increased susceptibility to stroke. KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases. Our goal is to identify potential biomarkers and genetic modifiers of CCMs, using a global comparative omics approach across several in vitro studies and multiple in vivo animal models. We hypothesize that through analysis of the CSC utilizing various omics, we can identify potential biomarkers and genetic modifiers, by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors.
Methods
We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic, transcriptomic, and proteomic levels to dissect alterations in various signaling cascades.
Results
Our analysis revealed a large set of genes that were validated across multiple independent studies, suggesting an important role for these identified genes in CCM pathogenesis.
Conclusion
This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models, allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs, which can be used for new therapeutic strategies.
Publisher
Springer Science and Business Media LLC
Subject
Neurology (clinical),Neurology,Surgery
Reference40 articles.
1. Otten P, Pizzolato GP, Rilliet B, Berney J. 131 cases of cavernous angioma (cavernomas) of the CNS, discovered by retrospective analysis of 24,535 autopsies. Neurochirurgie. 1989;35(2):82–3 128-31.
2. Cavalcanti DD, Kalani MY, Martirosyan NL, Eales J, Spetzler RF, Preul MC. Cerebral cavernous malformations: from genes to proteins to disease. J Neurosurg. 2012;116(1):122–32.
3. Batra S, Lin D, Recinos PF, Zhang J, Rigamonti D. Cavernous malformations: natural history, diagnosis and treatment. Nat Rev Neurol. 2009;5(12):659–70.
4. Rigamonti D, Spetzler RF, Drayer BP, Bojanowski WM, Hodak J, Rigamonti KH, et al. Appearance of venous malformations on magnetic resonance imaging. J Neurosurg. 1988;69(4):535–9.
5. Hayman LA, Evans RA, Ferrell RE, Fahr LM, Ostrow P, Riccardi VM. Familial cavernous angiomas: natural history and genetic study over a 5-year period. Am J Med Genet. 1982;11(2):147–60.