Proteomic profiling of acute stent thrombi reveals critical involvement of the complement system. (25th November 2020)

• Record Type: Journal Article
• Authors: Hofbauer, T.M; Distelmaier, K; Bileck, A; Ondracek, A.S; Seidl, V; Frueh, A; Neuditschko, B; Mangold, A; Pils, D; Gerner, C; Lang, I.M
• Is Part Of: European heart journal. Volume 41:(2020)Supplement 2
• Publication Date: 2020-11-25
• Subjects: Thrombosis, Platelets, and Coagulation; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/ehjci/ehaa946.1539
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Background: Stent thrombosis (ST) is a severe complication after primary percutaneous coronary intervention (pPCI) and associated with significant morbidity and mortality. Apart from procedure- and lesion-related parameters and patient-related factors. However, the underlying molecular and cellular mechanisms of ST are still not fully understood. Purpose: We aimed to perform in-depth proteomic analysis of ST to understand its pathogenesis. Methods: We recruited 77 patients suffering from ST after pPCI for myocardial infarction (MI). As controls, we included matched patients suffering from native vessel acute myocardial infarction (NT, n=154). Five cases of acute ST (within 24 h) and six cases of NT thrombi aspirated from the culprit site were subjected to shotgun proteomic analysis. Gene-set analysis was employed to screen for pathways differing between ST and NT. All-cause mortality was assessed using Kaplan-Meier analysis. Results: 9 patients presented with acute ST (<24 h, 11.7%), 18 patients with subacute ST (24 h to 30 days, 23.4%), 11 patients with late ST (30 days to 1 year, 14.3%) and 39 patients with very late ST (>1 year, 50.6%). ST was associated with increased all-cause mortality compared to NT (mean survival 129 vs. 109 months, log-rank p=0.032). We identified a total of 2438 proteins to be expressed in both ST and NT thrombi. Gene set analysis revealed the complement system to be highly active in acute ST compared to NT. Specifically, we found factors of both the classical (complement factor [C]1q, C1s) and alternative pathway (complement factor B) to be increased in ST, along with higher levels of C2, C3, C4a, C4b, C5, C8a and C9. Conclusion: This hypothesis-generating study highlights a crucial role of the complement system in the pathogenesis of acute ST. Further studies are required to validate these findings in a larger cohort. Funding Acknowledgement: Type of funding source: Public grant(s) – National budget only. Main funding source(s): Austrian Science Fund