From hemodynamic stress to inflammatory wall remodeling in intracranial aneurysms.

Abstract

Intracranial aneurysms are dynamic diseases of the cerebrovascular wall whose growth and rupture cannot be fully explained by size, location, or morphology. Accumulating evidence indicates that aneurysm progression involves coordinated changes in hemodynamic exposure, endothelial phenotype, immune-cell infiltration, vascular smooth muscle cell function, and the extracellular matrix. This review examines how abnormal flow is translated into inflammatory wall remodeling, with particular emphasis on endothelial-myeloid interactions and their downstream effects on mural-cell and matrix homeostasis. Disturbed hemodynamic environments can promote endothelial inflammatory activation and monocyte recruitment, while recruited macrophages adopt heterogeneous functional states that contribute to sustained inflammation, vascular smooth muscle cell dysfunction, and proteolytic injury. Recent single-cell and spatial studies further reveal extensive endothelial, myeloid, and mural-cell heterogeneity within the aneurysm wall. Progressive loss of vascular smooth muscle cell reparative capacity and altered extracellular matrix turnover may ultimately compromise matrix organization and local load-bearing integrity. We also discuss how vessel wall imaging, computational hemodynamics, circulating biomarkers, and omics approaches may help characterize biologically active aneurysms. Together, these findings support a regional view of intracranial aneurysm progression in which mechanical, inflammatory, and structural processes interact within a heterogeneous vessel wall.