Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO
Abstract Background Coronary microvascular obstruction (MVO) occurs in up to half of acute myocardial infarction patients receiving successful primary percutaneous coronary intervention (pPCI) and is associated with a much worse outcome. Whereas the fluid phase cross-talk between thrombosis and infl...
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BMC
2025-04-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-025-04694-9 |
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| author | Yu Qi Yufang Li Xuan Wei Han Wu Guannan Li Jianzhou Chen Lina Kang Kun Wang |
| author_facet | Yu Qi Yufang Li Xuan Wei Han Wu Guannan Li Jianzhou Chen Lina Kang Kun Wang |
| author_sort | Yu Qi |
| collection | DOAJ |
| description | Abstract Background Coronary microvascular obstruction (MVO) occurs in up to half of acute myocardial infarction patients receiving successful primary percutaneous coronary intervention (pPCI) and is associated with a much worse outcome. Whereas the fluid phase cross-talk between thrombosis and inflammation is well appreciated, the pathophysiological implication is still scant. Objectives This study sought to investigate the differentially expressed proteins and possible biological processes involved in MVO after pPCI in ST-segment elevation myocardial infarction (STEMI) patients based on thrombus proteomics. Methods Aspirated thrombi and pPCI from 16 STEMI patients within 12 h of symptom onset were collected, including 8 MI with MVO (MVO+) and 8 MI without MVO (MVO-). 4D label-free proteomics was used to explore the differentially expressed proteins. Gene ontology enrichment analysis was performed using Metascape software and protein‒protein interaction analysis was performed using Cystoscope software. Afterward, the Connectivity Map database was used to select drug candidates for MVO treatment. Results We identified a total of 471 proteins with expression changes greater than 1.5-fold at P < 0.05, of which 50 were significantly upregulated and 421 were downregulated in the MVO + group compared with the MVO- group. Gene ontology enrichment analysis of significant differentially expressed proteins revealed the central role of platelet activation and neutrophil degranulation processes in patients with MVO. The protein-protein interaction network also confirmed the significant interaction of inflammation and platelet activation, which may mediate the role of thrombus-inflammation in the pathogenesis of MVO. Drug screening revealed 4 drug candidates for MVO treatment: D-64,131, TC-1, SB-431,542 and alvespimycin. Conclusions Using the thrombus proteomic approach, we revealed the central role of the thrombus-inflammation interaction and potential drug candidates in STEMI with MVO. The findings from our study will contribute to the treatment of MVO in the future. |
| format | Article |
| id | doaj-art-95767b91bb514dbbad9dc0621c9745d7 |
| institution | DOAJ |
| issn | 1471-2261 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj-art-95767b91bb514dbbad9dc0621c9745d72025-08-20T03:04:59ZengBMCBMC Cardiovascular Disorders1471-22612025-04-0125111110.1186/s12872-025-04694-9Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVOYu Qi0Yufang Li1Xuan Wei2Han Wu3Guannan Li4Jianzhou Chen5Lina Kang6Kun Wang7Department of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityDepartment of Cardiology, Affiliated Hospital of Medical School, Nanjing Drum Tower Hospital, Nanjing UniversityAbstract Background Coronary microvascular obstruction (MVO) occurs in up to half of acute myocardial infarction patients receiving successful primary percutaneous coronary intervention (pPCI) and is associated with a much worse outcome. Whereas the fluid phase cross-talk between thrombosis and inflammation is well appreciated, the pathophysiological implication is still scant. Objectives This study sought to investigate the differentially expressed proteins and possible biological processes involved in MVO after pPCI in ST-segment elevation myocardial infarction (STEMI) patients based on thrombus proteomics. Methods Aspirated thrombi and pPCI from 16 STEMI patients within 12 h of symptom onset were collected, including 8 MI with MVO (MVO+) and 8 MI without MVO (MVO-). 4D label-free proteomics was used to explore the differentially expressed proteins. Gene ontology enrichment analysis was performed using Metascape software and protein‒protein interaction analysis was performed using Cystoscope software. Afterward, the Connectivity Map database was used to select drug candidates for MVO treatment. Results We identified a total of 471 proteins with expression changes greater than 1.5-fold at P < 0.05, of which 50 were significantly upregulated and 421 were downregulated in the MVO + group compared with the MVO- group. Gene ontology enrichment analysis of significant differentially expressed proteins revealed the central role of platelet activation and neutrophil degranulation processes in patients with MVO. The protein-protein interaction network also confirmed the significant interaction of inflammation and platelet activation, which may mediate the role of thrombus-inflammation in the pathogenesis of MVO. Drug screening revealed 4 drug candidates for MVO treatment: D-64,131, TC-1, SB-431,542 and alvespimycin. Conclusions Using the thrombus proteomic approach, we revealed the central role of the thrombus-inflammation interaction and potential drug candidates in STEMI with MVO. The findings from our study will contribute to the treatment of MVO in the future.https://doi.org/10.1186/s12872-025-04694-9STEMICMRMicrovascular obstructionThrombus‒inflammationProteomics |
| spellingShingle | Yu Qi Yufang Li Xuan Wei Han Wu Guannan Li Jianzhou Chen Lina Kang Kun Wang Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO BMC Cardiovascular Disorders STEMI CMR Microvascular obstruction Thrombus‒inflammation Proteomics |
| title | Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO |
| title_full | Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO |
| title_fullStr | Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO |
| title_full_unstemmed | Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO |
| title_short | Proteomic evaluation of the thrombosis-inflammation interplay in STEMI with MVO |
| title_sort | proteomic evaluation of the thrombosis inflammation interplay in stemi with mvo |
| topic | STEMI CMR Microvascular obstruction Thrombus‒inflammation Proteomics |
| url | https://doi.org/10.1186/s12872-025-04694-9 |
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