Peptidomic profiling of cerebrospinal fluid from patients with intracranial saccular aneurysms

Abstract

Intracranial saccular aneurysms (ISA) represent 90%-95% of all intracranial aneurysm cases, characterizing abnormal pockets at arterial branch points. Ruptures lead to subarachnoid hemorrhages (SAH) and poor prognoses. We applied mass spectrometry-based peptidomics to investigate the peptidome of twelve cerebrospinal fluid (CSF) samples collected from eleven patients diagnosed with ISA. For peptide profile analyses, participants were classified into: 1) ruptured intracranial saccular aneurysms (RIA), 2) unruptured intracranial saccular aneurysms (UIA), and late-ruptured intracranial saccular aneurysms (LRIA). Altogether, a total of 2199 peptides were detected by both Mascot and Peaks software, from which 484 (22.0%) were unique peptides. All unique peptides presented conserved chains, domains, regions of protein modulation and/or post-translational modification sites related to human diseases. Gene Ontology (GO) analyses of peptide precursor proteins showed that 42% are involved in binding, 56% in cellular anatomical entities, and 39% in intercellular signaling molecules. Unique peptides identified in patients diagnosed with RIA have a larger molecular weight and a distinctive developmental process compared to UIA and LRIA (P ≤ 0.05). Continued investigations will allow the characterization of the biological and clinical significance of the peptides identified in the present study, as well as identify prototypes for peptide-based pharmacological therapies to treat ISA. SIGNIFICANCE.

Keywords: Aneurysm; Biomarkers; Cerebrospinal fluid; InPeps; Intracellular peptides.