Evidence map›Paper›PMID 41410028›Full record

ArticleStroke2026

Trametinib Decreased Intracerebral Hemorrhages and Endothelial-to-Mesenchymal Transition in KRAS

Ohnmar Myint, Bridger H Freeman, Jaeyeong Jeong, Hyejin Park, Samantha M Wilfur, Shuning Huang, Jung-Eun Park, Jakob Körbelin, Jaroslaw Aronowski, Eun S Park and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Towards precision medicine for brain arteriovenous malformations.The Journal of clinical investigation · 2026
    Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Ohnmar Myint *Vivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0000-0001-9004-4282
Bridger H Freeman *Vivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.
Jaeyeong JeongVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0009-0006-5163-0004
Hyejin ParkVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0000-0002-5326-9711
Samantha M WilfurVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.
Shuning HuangDepartment of Diagnostic and Interventional Imaging, McGovern Medical School (S.H.), The University of Texas Health Science Center at Houston.
Jung-Eun ParkVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0009-0004-9216-3719
Jakob KörbelinDepartment of Oncology, Hematology and Bone Marrow Transplantation, University Medical Center Hamburg-Eppendorf, Germany (J.K.).ORCID 0000-0002-5435-7182
Jaroslaw AronowskiDepartment of Neurology, McGovern Medical School (J.A.), The University of Texas Health Science Center at Houston.ORCID 0000-0002-9256-7973
Eun S ParkVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0000-0002-4213-6681
Peng Roc ChenVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0000-0001-8438-132X
Eunhee KimVivian L. Smith Department of Neurosurgery, McGovern Medical School (O.M., B.H.F., J.J., H.P., S.M.W., J.E.P., E.S.P., P.R.C., E.K.), The University of Texas Health Science Center at Houston.ORCID 0000-0002-7755-7291

Funding

Microglia/macrophages as target to prevent intracerebral hemorrhage in KRAS mutation-induced brain arteriovenous malformationsR01NS126415 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Eunsu Park · 2022 to 2026
$1.9M
Endothelial-to-mesenchymal transition in mutant KRAS-induced brain as a cause of arteriovenous malformationsR01NS135153 · NINDS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Eunhee Kim · 2024 to 2026
$1.4M
NINDS NIH HHS R01 NS126415NINDS NIH HHS R01 NS135153
6 · The paper itself

Abstract

backgroundBrain arteriovenous malformations (bAVMs) are a major risk factor for intracerebral hemorrhages in young patients. Recent clinical studies have reported that the majority of human bAVMs harbor somatic KRAS (Kirsten rat sarcoma viral oncogene homolog) mutations. In our previous study, we confirmed the causal role of endothelial KRAS

methodsIn this study, we used the US Food and Drug Administration-approved MEK inhibitor, trametinib, to treat mice with bAVMs induced by brain endothelial cell (EC)-specific KRAS

resultsWe observed that trametinib significantly improved survivability, potentially through improved vessel integrity and reduction in the severity of bAVM ruptures. Our longitudinal observation of mice bAVMs using noninvasive magnetic resonance imaging revealed that trametinib decreased the total hemorrhagic volume at 8 weeks of treatment when administered at 1 mg/kg compared with the vehicle group, which was confirmed by histological analyses. In addition, trametinib altered endothelial-to-mesenchymal transition by reducing the expression levels of mesenchymal markers (N-Cad [N-cadherin], Slug, CD44 [cluster of differentiation 44]) and increasing an EC marker (VE-Cad [vascular endothelial cadherin]) in bAVMs of KRAS

conclusionsOur data demonstrate that trametinib improves bAVM pathology by reducing hemorrhagic risk and normalizing endothelial-to-mesenchymal transition. These findings suggest that trametinib is a promising agent to treat patients with bAVM.

Indexed as

Cerebral HemorrhageEpithelial-Mesenchymal TransitionIntracranial Arteriovenous MalformationsProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonesAnimalsEndothelial CellsMiceMice, TransgenicHras protein, mouseProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonestrametinibarteriovenous malformationscerebral hemorrhageendothelial cellsendothelial-mesenchymal transitiontrametinib

Identifiers

PMID41410028
PMCPMC12768455

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.