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

Eur Heart J. 2015 Apr 21;36(16):965-75. doi: 10.1093/eurheartj/ehu356. Epub 2014 Sep 12.

Abstract

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.

Keywords: Occlusive thrombus ageing; PCI; Platelets; Profilin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blood Platelets / pathology
  • Clopidogrel
  • Coronary Thrombosis / metabolism
  • Coronary Thrombosis / pathology*
  • Coronary Thrombosis / therapy
  • Female
  • Fibrinogen / metabolism
  • Humans
  • Leukocytes / pathology
  • Male
  • Middle Aged
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardial Infarction / therapy
  • Percutaneous Coronary Intervention
  • Platelet Aggregation / physiology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Profilins / metabolism*
  • Thrombectomy / methods
  • Thrombin / physiology
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Time-to-Treatment

Substances

  • Platelet Aggregation Inhibitors
  • Profilins
  • Fibrinogen
  • Clopidogrel
  • Thrombin
  • Ticlopidine