Changes in thrombus composition and profilin-1 release in acute myocardial infarction

Ilaria Ramaiola, Teresa Padró, Esther Peña, Oriol Juan-Babot, Judit Cubedo, Victoria Martin-Yuste, Manel Sabate, Lina Badimon

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    42 Citations (Scopus)

    Abstract

    © 2014 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com. Aim: Thrombus formation is a dynamic process regulated by flow, blood cells, and plasma proteins. The present study was performed to investigate the characteristics of human coronary thrombus in ST-segment elevation myocardial infarction (STEMI). Methods and results: Patients admitted with ST-elevation myocardial infarction, in which thrombectomy was performed, were included (n = 86). Intracoronary thrombi and blood from the culprit coronary site and the systemic circulation were obtained during percutaneous coronary intervention (PCI). Thrombi were categorized by onset-of-pain-to-PCI elapsed time in thrombus of <3 (T3) and more than 6 h of evolution (T6). Clinical, morphological, and proteomic variables were investigated. While T3 were mainly composed by platelets and fibrin(ogen), T6 were characterized by a reduced platelet content, increased leucocytes infiltration (including monocytes, neutrophils, T-cells, and B-cells), and appearance of undifferentiated progenitor cells. Significant differences between T3 and T6 were found in the cell cytoskeleton-associated proteome (beta-actin and tropomyosin 3 and 4). By discovery proteomics, we have identified profilin-1 (Pfn-1) in the coronary thrombi and detected higher levels in T3 than in T6. While plasma Pfn-1 levels were low in T3 patients, levels significantly increased in both coronary and peripheral circulation in T6 patients indicating release. In vitro platelet aggregation studies showed that platelets secrete Pfn-1 upon complete activation. Conclusion: Coronary thrombi show rapid dynamic changes both in structure and cell composition as a function of elapsed onset-of-pain-to-PCI time. Aged ischaemic thrombi were more likely to have reduced Pfn-1 content releasing Pfn-1 to the circulation. Onset-of-pain-to-PCI elapsed time in STEMI patients and hence age of occlusive thrombus can be profiled by Pfn-1 levels found in the peripheral circulation.
    Original languageEnglish
    Pages (from-to)965-975
    JournalEuropean Heart Journal
    Volume36
    Issue number16
    DOIs
    Publication statusPublished - 21 Apr 2015

    Keywords

    • Occlusive thrombus ageing
    • PCI
    • Platelets
    • Profilin-1

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