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Selective Endothelial Hyperactivation of Oncogenic KRAS Induces Brain Arteriovenous Malformations in Mice by Eun S. Park; Sehee Kim; Shuning Huang; Ji Young Yoo; Jakob Körbelin; Tae Jin Lee; Balveen Kaur; Pramod K. Dash; Peng R. Chen; Eunhee Kim is a Medicine article available to read on EtoBox.
What is Selective Endothelial Hyperactivation of Oncogenic KRAS Induces Brain Arteriovenous Malformations in Mice about?
## Objective Brain arteriovenous malformations (bAVMs) are a leading cause of hemorrhagic stroke and neurological deficits in children and young adults, however, no pharmacological intervention is available to treat these patients. Although more than 95% of bAVMs are sporadic without family history, the pathogenesis of sporadic bAVMs is largely unknown, which may account for the lack of therapeutic options. KRAS mutations are frequently observed in cancer, and a recent unprecedented finding of these mutations in human sporadic bAVMs offers a new direction in the bAVM research. Using a novel adeno‐associated virus targeting brain endothelium (AAV‐BR1), the current study tested if endothelial KRAS^G12V^ mutation induces sporadic bAVMs in mice. ## Methods Five‐week‐old mice were systemically injected with either AAV‐BR1‐GFP or ‐KRAS^G12V^. At 8 weeks after the AAV injection, bAVM formation and characteristics were addressed by histological and molecular analyses. The effect of MEK/ERK inhibition on KRAS^G12V^‐induced bAVMs was determined by treatment of trametinib, a US Food and Drug Administration (FDA)‐approved MEK/ERK inhibitor. ## Results The viral‐mediated KRAS^G12V^ overexpressi
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- Author
- Eun S. Park; Sehee Kim; Shuning Huang; Ji Young Yoo; Jakob Körbelin; Tae Jin Lee; Balveen Kaur; Pramod K. Dash; Peng R. Chen; Eunhee Kim
- Publisher
- Wiley
- Published
- 2021
- Language
- EN
- Field
- Medicine (Health Sciences)