Imaging mass spectroscopy delineates the thinned and thickened walls of intracranial aneurysms

Abstract

Object: The wall thickness of intracranial aneurysms (IAs) is heterogeneous. Although thinning of the IA wall is thought to contribute to IA rupture, the underlying mechanism remains poorly understood. Recently, imaging mass spectroscopy (IMS) has been used to reveal the distribution of phospholipids in vascular diseases. To investigate the feature of phospholipid composition of IA walls, we conducted IMS in a rat model of experimentally induced IA.

Material and methods: IAs were surgically induced in 7-week-old male rats and analyzed by IMS in negative-ion mode.

Results: A molecule at m/z 885.5 was more abundant in the thickened wall than in the thinned wall (P = 0.03). Multiple-stage mass spectroscopy revealed the molecule to be phosphatidylinositol containing stearic acid and arachidonic acid (PI 18:0/20:4). Immunohistochemistry indicated that vascular smooth muscle cells (SMCs) in the thickened wall had dedifferentiated phenotypes. To investigate the relationship between accumulation of PI (18:0/20:4) and phenotypic changes in SMCs, we subjected primary mouse aortic SMCs to liquid chromatography-tandem mass spectrometry. Notably, dedifferentiated SMCs had 1.3-fold more PI (18:0/20:4) than partly differentiated SMCs.

Conclusions: Our study demonstrated the heterogeneity in phospholipid composition of the aneurysmal walls using experimentally induced IAs. PI (18:0/20:4) accumulated at high levels in the thickened aneurysmal wall where synthetic dedifferentiated SMCs exist, suggesting that this phospholipid may be involved in the phenotypic switching of medial SMCs in the IA wall.

Keywords: Imaging mass spectroscopy; Intracranial aneurysm; Phenotype; Phosphatidylinositol; Vascular smooth muscle cell.