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Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study

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submitted on 2024-08-05, 11:29 and posted on 2024-08-05, 11:30 authored by Shahnaz Qadri, Muhamad U. Sohail, Naveed Akhtar, Ghulam Jeelani Pir, Ghada Yousif, Sajitha V. Pananchikkal, Muna Al-Noubi, Sunkyu Choi, Ashfaq Shuaib, Yousef Haik, Aijaz Parray, Frank Schmidt

Acute ischemic stroke is the most common cause of neurologic dysfunction caused by focal brain ischemia and tissue injury. Diabetes is a major risk factor of stroke, exacerbating disease management and prognosis. Therefore, discovering new diagnostic markers and therapeutic targets is critical for stroke prevention and treatment. Extracellular vesicles (EVs), with their distinctive properties, have emerged as promising candidates for biomarker discovery and therapeutic application. This case-control study utilized mass spectrometry-based proteomics to compare EVs from non-diabetic stroke (nDS = 14), diabetic stroke (DS = 13), and healthy control (HC = 12) subjects. Among 1288 identified proteins, 387 were statistically compared. Statistical comparisons using a general linear model (log2 foldchange ≥0.58 and FDR-p≤0.05) were performed for nDS vs HC, DS vs HC, and DS vs nDS. DS vs HC and DS vs nDS comparisons produced 123 and 149 differentially expressed proteins, respectively. Fibrinogen gamma chain (FIBG), Fibrinogen beta chain (FIBB), Tetratricopeptide repeat protein 16 (TTC16), Proline rich 14-like (PR14L), Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKE), Biorientation of chromosomes in cell division protein 1-like 1 (BD1L1), and protein PR14L exhibited significant differences in the DS group. The pathway analysis revealed that the complement system pathways were activated, and blood coagulation and neuroprotection were inhibited in the DS group (z-score ≥2; p ≤ 0.05). These findings underscore the potential of EVs proteomics in identifying biomarkers for stroke management and prevention, warranting further clinical investigation.

Other Information

Published in: Frontiers in Molecular Biosciences
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3389/fmolb.2024.1387859

Funding

Qatar National Research Fund (NPRP11S-0114-180289), Diabetes and hypertension contribute to cerebral small vessel disease via enhanced activity of biomarkers, microparticles and exosomes: A prospective study in stroke patients and age-matched controls.

Qatar National Research Fund (NPRP12S-0318-190392), Revealing the potential of pathogen-specific antibodies in diabetes patients with the aim of obtaining new diagnostic and prognostic signatures.

History

Language

  • English

Publisher

Frontiers

Publication Year

  • 2024

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • College of Science and Engineering - HBKU
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC
  • Weill Cornell Medicine - Qatar