Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment

Tsung-Heng Lee; Chih-Ning Cheng; Chung-Wei Lee; Ching-Hua Kuo; Sung-Chun Tang; Jiann-Shing Jeng

doi:10.1016/j.jfma.2022.08.021

Investigating sphingolipids as biomarkers for the outcomes of acute ischemic stroke patients receiving endovascular treatment

J Formos Med Assoc. 2023 Jan;122(1):19-28. doi: 10.1016/j.jfma.2022.08.021. Epub 2022 Sep 30.

Authors

Tsung-Heng Lee¹, Chih-Ning Cheng¹, Chung-Wei Lee², Ching-Hua Kuo³, Sung-Chun Tang⁴, Jiann-Shing Jeng⁵

Affiliations

¹ School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.
² Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan.
³ School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan; The Metabolomics Core Laboratory, Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: kuoch@ntu.edu.tw.
⁴ Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: sctang@ntuh.gov.tw.
⁵ Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.

PMID: 36184387
DOI: 10.1016/j.jfma.2022.08.021

Abstract

Background: Long-chain ceramides are associated with the mechanisms and clinical outcomes of acute ischemic stroke (AIS). This study aimed to investigate the plasma ceramides and sphingosine-1-phosphate in AIS patients undergoing endovascular thrombectomy (EVT) and their associations with outcomes.

Methods: Plasma samples were collected from 75 AIS patients who underwent EVT before (T1), immediately after (T2), and 24 h after (T3) the procedures and 19 controls that were matched with age, sex, and co-morbidities. The levels of ceramides with different fatty acyl chain lengths and sphingosine-1-phosphate were measured by UHPLC-ESI-MS/MS. A poor outcome was defined as a modified Rankin Scale score of 3-6 at 3 months after stroke.

Results: The plasma levels of long-chain ceramides Cer (d18:1/16:0) at all three time points, Cer (d18:1/18:0) at T1 and T3, and Cer (d18:1/20:0) at T1 and very-long-chain ceramide Cer (d18:1/24:1) at T1 were significantly higher in AIS patients than those in the controls. In contrast, the plasma levels of sphingosine-1-phosphate in AIS patients were significantly lower than those in the controls at all three time points. Among the AIS patients, 34 (45.3%) had poor functional outcomes at 3 months poststroke. Multivariable analysis showed that higher levels of Cer (d18:1/16:0) and Cer (d18:1/18:0) at all three time points, Cer (d18:1/20:0) at T1 and T2, and Cer (d18:1/24:0) at T2 remained significantly associated with poor functional outcomes after adjustment for potential confounding factors.

Conclusion: Plasma ceramides were elevated early in AIS patients with acute large artery occlusion. Furthermore, Cer (d18:1/16:0) and Cer (d18:1/18:0) could be early prognostic indicators for AIS patients undergoing EVT.

Keywords: Acute ischemic stroke; Ceramides; Endovascular thrombectomy; Prognostic markers; Sphingosine-1-phosphate.

MeSH terms

Biomarkers
Ceramides / analysis
Endovascular Procedures*
Humans
Ischemic Stroke* / surgery
Sphingolipids
Stroke*
Tandem Mass Spectrometry / methods

Substances

Sphingolipids
sphingosine 1-phosphate
Ceramides
Biomarkers