Exosomal miR-154-5p derived from oxidatively stressed vascular smooth muscle cells promotes the intracranial aneurysm phenotype in recipient vascular smooth muscle cells by targeting myosin light chain kinase, identifying it as a novel potentially associated and promising therapeutic target for intracranial aneurysm management.
miR-154-5p expression is upregulated in intracranial aneurysm specimens compared to controls.
miR-154-5p promotes the intracranial aneurysm phenotype in vascular smooth muscle cells (VSMCs).
H2O2-exposed VSMCs secrete exosomal miR-154-5p that can be transferred to other VSMCs.
Exosomal miR-154-5p promotes the intracranial aneurysm phenotype in VSMCs by targeting myosin light chain kinase (MLCK).
Exosomal miR-154-5p is identified as a novel potentially associated and promising therapeutic target for intracranial aneurysm management.
This research investigated how tiny RNA molecules called microRNAs, packaged inside nano-sized vesicles called exosomes, may contribute to the development of intracranial aneurysms — dangerous bulges in brain blood vessels that can rupture and cause life-threatening bleeding. The researchers found that a specific microRNA, miR-154-5p, was more abundant in aneurysm tissue than in normal tissue. They also found that when vascular smooth muscle cells (the cells that make up blood vessel walls) were exposed to oxidative stress — the kind of cellular damage associated with aneurysm development — they released exosomes containing miR-154-5p. These exosomes were then taken up by neighboring smooth muscle cells, spreading the disease-promoting signal from cell to cell. The study further identified that miR-154-5p works by suppressing a protein called myosin light chain kinase (MLCK), which normally helps regulate the structural integrity and contractility of blood vessel walls. By targeting MLCK, miR-154-5p appears to push smooth muscle cells toward a dysfunctional state associated with aneurysm formation. The researchers confirmed this connection using multiple laboratory techniques including RNA pull-down and luciferase reporter assays. This research suggests that exosomal miR-154-5p and its target MLCK represent a previously unrecognized communication pathway that may drive intracranial aneurysm progression. These findings could point toward new diagnostic or therapeutic targets for a condition that currently has limited non-surgical treatment options. However, the authors note that all experiments were conducted in cell cultures (in vitro), meaning further research in animal models and eventually humans would be needed to determine whether these findings translate to real-world clinical applications.
Song J, Luan W, Chu L, Pan P, Qian Y, Lu Y. (2026). Exosomal micro ribonucleic acid-154-5p derived from vascular smooth muscle cell mediates intracranial aneurysm phenotype in vitro via myosin light chain kinase targeting.. The Journal of international medical research. https://doi.org/10.1177/03000605261483185