Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke
Abstract Acute 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 remain...
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| Format: | Article |
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Wiley
2024-12-01
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| Series: | MedComm – Future Medicine |
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| Online Access: | https://doi.org/10.1002/mef2.70002 |
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| author | Hong‐Xia Li Ying‐Ying Han Hong‐Xiang Yu Lu‐Feng Wang Can Cui Ling‐Ting Jin Meng‐Ru Ge Xue Gao Gang Li Yong‐Bo Hu Bei Zhang |
| author_facet | Hong‐Xia Li Ying‐Ying Han Hong‐Xiang Yu Lu‐Feng Wang Can Cui Ling‐Ting Jin Meng‐Ru Ge Xue Gao Gang Li Yong‐Bo Hu Bei Zhang |
| author_sort | Hong‐Xia Li |
| collection | DOAJ |
| description | Abstract Acute 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. |
| format | Article |
| id | doaj-art-ae1abbf089a24cd9b42036d3a10f3a0a |
| institution | OA Journals |
| issn | 2769-6456 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm – Future Medicine |
| spelling | doaj-art-ae1abbf089a24cd9b42036d3a10f3a0a2025-08-20T02:38:59ZengWileyMedComm – Future Medicine2769-64562024-12-0134n/an/a10.1002/mef2.70002Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic strokeHong‐Xia Li0Ying‐Ying Han1Hong‐Xiang Yu2Lu‐Feng Wang3Can Cui4Ling‐Ting Jin5Meng‐Ru Ge6Xue Gao7Gang Li8Yong‐Bo Hu9Bei Zhang10Department of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaDepartment of Neurology the First Affiliated Hospital of Naval Medical University (Shanghai Changhai Hospital) Shanghai ChinaDepartment of Neurology, Shanghai East Hospital, School of Medicine Tongji University. Shanghai ChinaAbstract Acute 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.https://doi.org/10.1002/mef2.70002acute ischemic strokeHashimoto's thyroiditisMendelian randomizationtandem mass tag proteomicsthyroid dysfunction |
| spellingShingle | Hong‐Xia Li Ying‐Ying Han Hong‐Xiang Yu Lu‐Feng Wang Can Cui Ling‐Ting Jin Meng‐Ru Ge Xue Gao Gang Li Yong‐Bo Hu Bei Zhang Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke MedComm – Future Medicine acute ischemic stroke Hashimoto's thyroiditis Mendelian randomization tandem mass tag proteomics thyroid dysfunction |
| title | Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| title_full | Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| title_fullStr | Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| title_full_unstemmed | Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| title_short | Combined Mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| title_sort | combined mendelian randomization and quantitative proteomics analysis to study the influence of thyroid dysfunction on acute ischemic stroke |
| topic | acute ischemic stroke Hashimoto's thyroiditis Mendelian randomization tandem mass tag proteomics thyroid dysfunction |
| url | https://doi.org/10.1002/mef2.70002 |
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