Peptidomic profiling of cerebrospinal fluid from patients with intracranial saccular aneurysms

Author(s)

Sakaya, Gabriel R. ^[1] ; Parada, Carolina A. ^[2] ; Eichler, Rosangela A. ^[2] ; Yamaki, Vitor N. ^[1] ; Navon, Ami ^[3] ; Heimann, Andrea S. ^[4] ; Figueiredo, Eberval G. ^[1] ; Ferro, Emer S. ^{[2, 3]}

Affiliation

^[1] Univ Sao Paulo, Sch Med, Div Neurol Surg, BR-05403000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Biomed Sci Inst, Dept Pharmacol, BR-05508000 Sao Paulo, SP - Brazil

^[3] Weizmann Inst Sci, Dept Biol Regulat, IL-7610001 Rehovot - Israel

^[4] Proteimax Israel Biotechnol, IL-61000 Tel Aviv - Israel

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 240, MAY 30 2021.
• Web of Science Citations: 0

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: Intracranial aneurysms (IAs) are arterial dilations that occur due to weakness in the media layer of the arterial wall. Due to lack of symptoms, IAs are usually found incidentally when the rupture occurs. The mechanism that causes vasospasms are not completely understood. Here, twelve cerebrospinal fluid (CSF) samples collected from eleven patients diagnosed with IAs were investigated by mass spectrometry-based peptidomics. 2199 peptides were identified by both Mascot and Peaks software, from which 484 (22.0%) were unique peptides. Even considering the relatively low number of patients enrolled in this seminal study, 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). These results suggest peptides as novel ISA markers. Continued investigations will allow the undoubted characterization of specific peptides that can be used as prototypes for peptide-based diagnostics and pharmacological therapies, to predict, prevent and/or treat ISA. (AU)

• FAPESP's process: 16/04000-3 - Pharmacology of oligopeptidases and intracellular peptides
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/07332-5 - Structural basis of intracellular peptides-protein interactions
• Grantee: Carolina Angelica da Silva Parada
• Support Opportunities: Scholarships in Brazil - Post-Doctoral