Discovery and validation of circulating stroke metabolites by NMR-based analyses using patients from the MISS and UK Biobank

Madhusmita Rout; April Vaughan; Apple Blair; Stavros Stavrakis; Evgeny V Sidorov; Dharambir K Sanghera

doi:10.1016/j.neuint.2023.105588

Discovery and validation of circulating stroke metabolites by NMR-based analyses using patients from the MISS and UK Biobank

Neurochem Int. 2023 Oct:169:105588. doi: 10.1016/j.neuint.2023.105588. Epub 2023 Jul 26.

Authors

Madhusmita Rout¹, April Vaughan², Apple Blair², Stavros Stavrakis³, Evgeny V Sidorov², Dharambir K Sanghera⁴

Affiliations

¹ Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
² Department of Neurology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
³ Department of Cardiology, Oklahoma University of Health Sciences Center, Oklahoma City, OK, USA.
⁴ Department of Pediatrics, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Pharmaceutical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Department of Physiology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. Electronic address: Dharambir-Sanghera@ouhsc.edu.

PMID: 37499945
DOI: 10.1016/j.neuint.2023.105588

Abstract

Background: Stroke is a significant health issue in the United States, and identifying biomarkers for the prevention and functional recovery after an acute stroke remains the highest priority. This study aims to identify circulating metabolite signatures that may be associated with stroke pathophysiology by performing discovery and validation studies.

Methods: We performed targeted metabolomics profiling of 420 participants of the discovery dataset of Metabolome in an Ischemic Stroke Study (MISS) using high-throughput nuclear magnetic resonance (NMR) spectroscopy. A validation study of significantly altered metabolites was conducted using an independent cohort of 117,988 participants from the UK Biobank, whose metabolomics profiles were generated using the same NMR technology.

Results and conclusion: Our study identified 16 metabolites to be significantly perturbed during acute stroke. Amino acid phenylalanine was significantly increased, while glutamine and histidine were significantly lowered in stroke. Serum levels of apolipoprotein A-1, HDL particles, small HDL particles, essential fatty acids, and phosphatidylcholine were reduced, while ketone bodies like 3-hydroxybutyrate and acetoacetate were markedly increased in stroke. Based on the robust validation in a large independent UK Biobank dataset, some of these analytes may become clinically meaningful biomarkers to predict or prevent stroke in humans.

Keywords: Acute stroke; Amino acids; Apolipoproteins; Fatty acids; Ketone bodies.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Biological Specimen Banks
Biomarkers
Humans
Ischemic Stroke*
Magnetic Resonance Spectroscopy / methods
Metabolome
Metabolomics / methods
Stroke*
United Kingdom / epidemiology

Substances

Biomarkers

Grants and funding

R01 DK118427/DK/NIDDK NIH HHS/United States