High importance
Sep 17, 2026
To explore the role of extracellular matrix remodeling and internal elastic lamina (IEL) alterations in cerebral arteriovenous malformations (cAVMs) and their contributions to vascular wall biology and structural stability.
A structured qualitative literature review and narrative synthesis was conducted, analyzing histological, molecular, and genetic studies pertaining to elastin biology, IEL structure, and extracellular matrix remodeling in cAVMs.
Forty-three studies were reviewed, revealing direct histopathological evidence of IEL fragmentation in only two. Other studies identified structural abnormalities such as IEL disorganization and dysregulated signaling pathways (KRAS-MAPK, Notch, BMP9/ALK1) associated with vascular endothelial homeostasis and remodeling, although most did not specifically evaluate IEL architecture.
The substantial methodological and biological heterogeneity across the included studies limited the ability to perform a quantitative meta-analysis. The findings mainly support biological plausibility without establishing causal relationships between IEL alterations and cAVM pathogenesis or rupture susceptibility.
Understanding the mechanisms behind IEL and extracellular matrix alterations in cAVMs could shed light on potential therapeutic targets and enhance the understanding of vascular stability, informing treatment strategies for conditions like Hereditary Hemorrhagic Telangiectasia (HHT) and related vascular anomalies.
Cerebral arteriovenous malformations (cAVMs) are high-flow vascular lesions associated with a relevant risk of intracranial hemorrhage. Beyond angioarchitectural determinants, emerging evidence suggests that alterations of the internal elastic lamina (IEL) and elastic fiber network may contribute to vascular remodeling and structural instability. We conducted a structured qualitative literature review with narrative synthesis, without quantitative meta-analysis because of substantial methodological and biological heterogeneity across studies. We included histological, molecular, and genetic investigations addressing elastin biology, IEL structure, extracellular matrix remodeling, and related signaling pathways in cAVMs within the broader context of vascular wall biology. Twenty studies met the predefined inclusion criteria. Direct histopathological evidence of IEL fragmentation was identified in only two primary studies, whereas additional histological investigations reported structural abnormalities including IEL disorganization, interruption, or irregular thickening. Molecular studies consistently described dysregulation of KRAS-MAPK, Notch, and BMP9/ALK1 signaling pathways involved in vascular endothelial homeostasis and extracellular matrix remodeling, although most did not directly evaluate IEL or elastic fiber architecture. Collectively, these findings support biologically plausible mechanisms of vascular remodeling rather than a unified mechanistic cascade. Similarities with inherited disorders affecting elastogenesis represent mechanistic analogies rather than evidence of shared disease pathogenesis. Alterations of the IEL and elastic fiber network may represent a relevant component of the structural phenotype of cAVMs, potentially acting as downstream or parallel manifestations within a multifactorial biological framework. Integrating histopathological and molecular evidence may improve the biological characterization of these lesions and support future hypothesis generation regarding vascular stability. However, the currently available evidence does not allow causal inference regarding the role of IEL alterations or elastic fiber disruption in cAVM pathogenesis or rupture susceptibility.