Gene regulation and arterial wall regeneration in intracranial aneurysms
Year: 2026
Type: article
Abstract: Background: Intracranial aneurysms exhibit endothelial injury, smooth muscle depletion, elastic lamina disruption, and collagen remodeling. Whether genetic intervention can restore the native wall and reverse an established lesion remains uncertain. Objective: To evaluate evidence for gene-regulated regeneration of established intracranial saccular aneurysms and define experimental criteria for demonstrating functional arterial reconstruction. Methods: A targeted narrative review of PubMed records and accessible primary publications was undertaken through 15 October 2026. Intracranial intervention experiments, human tissue studies, and extracranial mechanistic evidence were evaluated separately. Evidence synthesis: A delayed-treatment rat study reported intracranial aneurysm regression after combined nuclear factor kappa B and ETS inhibition. Tropoelastin gene transfer and matrix-directed interventions produced regression or structural recovery in experimental abdominal aortic aneurysms. Intracranial studies support SOX17-associated endothelial integrity and SIRT1-associated rupture protection. A 2026 human cellular atlas identified smooth muscle depletion, activated perivascular fibroblasts, and inflammatory macrophage programs. These observations support a coordinated repair hypothesis but do not establish a therapeutic gene combination that restores normal cerebral arterial architecture. Conclusions: Gene-regulated aneurysm wall reconstruction is biologically plausible but unproven. Demonstration requires pretreatment confirmation of an established lesion, durable sac regression, newly organized endothelial and medial compartments, appropriately positioned elastic matrix, improved mechanical function, and preserved parent and branch vessels. Molecular improvement, wall thickening, or angiographic occlusion alone cannot establish regeneration. Component-controlled studies are needed before clinical translation. Keywords: Intracranial aneurysm; gene therapy; vascular smooth muscle; extracellular matrix; elastin; CRISPR activation; vascular regeneration.
Author: Lanka, Gandhi Bhaskar Patrudu
Institution: King George Hospital
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7222575147