Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke

Hong‐Xia Li; Ying‐Ying Han; Haonan Yu; Lu‐Feng Wang; Can Cui; Ling‐Ting Jin; Meng‐Ru Ge; Xue Gao; Gang Li; Yong‐Bo Hu; Bei Zhang

doi:10.1002/mef2.70002

journal article Open Access Nov 19, 2024

Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke

Hong‐Xia Li Ying‐Ying Han Haonan Yu

Lu‐Feng Wang Can Cui

Ling‐Ting Jin Meng‐Ru Ge Xue Gao

Gang Li

Yong‐Bo Hu Bei Zhang

MedComm – Future Medicine Vol. 3 No. 4 · Wiley

View at Publisher Save 10.1002/mef2.70002

Abstract

AbstractAcute ischemic stroke (AIS) is characterized by high morbidity and mortality, making it crucial to identify the risk factors that influence its occurrence and prognosis. Although individuals with thyroid dysfunction exhibit altered stroke patterns, evidence from observational studies remains inconsistent. Herein, we investigated the influence of thyroid dysfunction on stroke progression and prognosis. We combined Mendelian randomization (MR) and tandem mass tag (TMT)‐based quantitative proteomics analysis to study the influence of thyroid dysfunction on AIS. Differentially expression proteins (DEPs) were subsequently identified, functional enrichment analysis was performed, and a protein–protein interaction (PPI) network was constructed. Protein alterations were further validated by western blot. MR analysis revealed a causal association between thyroid disorders and ischemic stroke. DEP analysis identified 38 downregulated proteins and five upregulated proteins. Functional enrichment analysis and PPI network construction highlighted the importance of immune response activation and acute phase pathways, along with the suppression of focal adhesion, regulation of the actin cytoskeleton, and platelet activation pathways. Vasodilator‐stimulated phosphoprotein, MYL12B, MYL6, and TPM4 were identified as key DEPs significantly associated with pathological pathways and were verified by western blot. The identification of these key proteins and pathways provides new perspectives for investigating the progression and prognosis of AIS.

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Published: Nov 19, 2024
Vol/Issue: 3(4)
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Hong‐Xia Li