Tsung-Heng Lee1, Chih-Ning Cheng1, Hsi-Chun Chao1, Ching-Hua Lee1, Ching-Hua Kuo2, Sung-Chun Tang3, Jiann-Shing Jeng4. 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. 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. 3. Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan. Electronic address: sctang@ntuh.gov.tw. 4. Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Abstract
BACKGROUND/ PURPOSE: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes. METHODS: Plasma samples were collected from patients with AIS at <48 and 48-72 h post stroke and from nonstroke controls. The levels of S1P and ceramides with different fatty acyl chain lengths were measured by the ultra-high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). A poor functional outcome was defined as a modified Rankin Scale (mRS) score ≥2 at 3 months after AIS. RESULTS: The results showed that S1P and very-long-chain ceramides were significantly decreased in AIS patients (n = 87; poor outcome, 56.3%) compared to nonstroke controls (n = 30). In contrast, long-chain ceramides were significantly increased in AIS patients. More importantly, higher levels of Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/22:0) at 48-72 h were significantly associated with poor functional outcomes after adjusting for potential clinical confounders, including age, sex, hypertension, and National Institutes of Health Stroke Scale score at admission. CONCLUSION: Our study supported the dynamic metabolism of sphingolipids after the occurrence of AIS. Ceramides could be potential prognostic markers for patients with AIS.
BACKGROUND/ PURPOSE: Sphingolipids are major constituents of eukaryotic cell membranes and play key roles in cellular regulatory processes. Our recent results in an experimental stroke animal model demonstrated changes in sphingolipids in response to acute ischemic brain injury. This study aimed to investigate the plasma levels of sphingosine-1-phosphate (S1P) and ceramides in acute ischemic stroke (AIS) patients and their associations with functional outcomes. METHODS: Plasma samples were collected from patients with AIS at <48 and 48-72 h post stroke and from nonstroke controls. The levels of S1P and ceramides with different fatty acyl chain lengths were measured by the ultra-high-pressure liquid chromatography-electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). A poor functional outcome was defined as a modified Rankin Scale (mRS) score ≥2 at 3 months after AIS. RESULTS: The results showed that S1P and very-long-chain ceramides were significantly decreased in AIS patients (n = 87; poor outcome, 56.3%) compared to nonstroke controls (n = 30). In contrast, long-chain ceramides were significantly increased in AIS patients. More importantly, higher levels of Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/22:0) at 48-72 h were significantly associated with poor functional outcomes after adjusting for potential clinical confounders, including age, sex, hypertension, and National Institutes of Health Stroke Scale score at admission. CONCLUSION: Our study supported the dynamic metabolism of sphingolipids after the occurrence of AIS. Ceramides could be potential prognostic markers for patients with AIS.
Authors: Alberto Ouro; Clara Correa-Paz; Elena Maqueda; Antía Custodia; Marta Aramburu-Núñez; Daniel Romaus-Sanjurjo; Adrián Posado-Fernández; María Candamo-Lourido; Maria Luz Alonso-Alonso; Pablo Hervella; Ramón Iglesias-Rey; José Castillo; Francisco Campos; Tomás Sobrino Journal: Front Mol Biosci Date: 2022-04-20
Authors: Sonia Borodzicz-Jażdżyk; Piotr Jażdżyk; Wojciech Łysik; Agnieszka Cudnoch-Jȩdrzejewska; Katarzyna Czarzasta Journal: Front Cardiovasc Med Date: 2022-08-31