Therapeutic potential and pathophysiological role of vitamin D in cerebral cavernous malformations: Systematic review of preclinical and clinical evidence
Alomari O, Eyvazova H, Yılmaz BN, Hamamreh R, Alomari T, Hatip A, Reiter RJ
Clinical neurology and neurosurgery · 0 citas
Etiquetas de revisión
Financiación no declaradaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Revisión sistemática (indexado por PubMed)
- Estudiado en
- Personas, más trabajo en animales o laboratorio
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación no declarada
Publicación
- Publicado
- 2026-06-21 · Clin Neurol Neurosurg · vol. 269 · pág. 109550
- Editorial
- Elsevier BV
- Citado
- 1 cita · más que el 89% de estudios similares · 2.5× el promedio de su campo
- Referencias
- 57 trabajos
- Acceso
- Acceso abierto (copia en repositorio) · CC-BY-NC-ND
- Áreas de investigación
- Vascular Malformations Diagnosis and Treatment · Vitamin D Research Studies · Vascular Malformations and Hemangiomas
- Palabras clave
- cerebral cavernous malformations, vitamin D, vitamin D receptor, RhoA/ROCK signaling, 25-hydroxyvitamin D, vitamin D3 supplementation, CYP27A1, CYP27B1, oxidative stress, autophagy, mTORC1, hemorrhage, blood-brain barrier, disease-modifying therapy, genetic polymorphism
- MeSH
- animals, humans, hemangioma, cavernous, central nervous system, vitamin d, receptors, calcitriol, signal transduction
7 autores
- Omar Alomarı🇹🇷 · autor de correspondenciaSağlık Bilimleri Üniversitesi
- Habiba Eyvazova🇹🇷Sağlık Bilimleri Üniversitesi
- B Yilmaz🇹🇷Sağlık Bilimleri Üniversitesi
- Rawan Hamamreh🇯🇴Hashemite University
- Tasneem Alomari🇯🇴Jordan University of Science and Technology
- Abdullah Hatip🇹🇷Fırat University
- Russel J. Reiter🇺🇸The University of Texas at San Antonio Health Science Center
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background and purpose
Cerebral cavernous malformations (CCMs) are vascular lesions characterized by blood-brain barrier instability and a propensity for recurrent hemorrhage. While RhoA-ROCK signaling dysregulation is the canonical driver of pathogenesis, vitamin D has emerged as a potential molecular modifier. This systematic review synthesizes clinical, genetic, and preclinical evidence to evaluate the biological role of vitamin D and its receptor signaling pathways in CCM pathogenesis.
Methods
Following PRISMA guidelines, a comprehensive search was conducted across MEDLINE, EMBASE, Web of Science, and Scopus through February 2026. Eligible studies included clinical cohorts, genetic association analyses, and preclinical models investigating vitamin D signaling in CCM. Quality assessment was performed using NIH, JBI, and SYRCLE tools.
Results
Nine studies representing 971 patients and several preclinical models were included. Observational clinical data indicate that lower serum 25-hydroxyvitamin D (25(OH)D) levels are associated with "chronically aggressive" disease phenotypes and hemorrhagic presentation, though these findings are limited to small, associative cohorts. Genetically, polymorphisms in the vitamin D receptor (VDR) and metabolic enzymes (CYP27A1, CYP27B1) correlate with clinical heterogeneity and lesion burden. Mechanistically, preclinical cell and animal models demonstrate that vitamin D can non-canonically inhibit the RhoA-ROCK axis, reduce local oxidative stress, and induce autophagy via mTORC1 inhibition. In specific murine models, cholecalciferol supplementation reduced lesion burden by approximately 50%.
Conclusions
Circulating vitamin D status and related genetic variants serve as hypothesis-generating biological correlates of CCM disease activity, but causality has not been established and current evidence is insufficient to recommend supplementation to alter clinical outcomes. While the VDR pathway constitutes a plausible molecular axis associated with endothelial structural homeostasis, routine clinical supplementation with a disease-modifying intent must await prospective, randomized controlled trials to formally establish safety and therapeutic efficacy.
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