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 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-64131, TC-1, SB-431542 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.