title: Changes in thrombus composition and profilin-1 release in acute myocardial infarction.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ramaiola
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Peña
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Juan-Babot
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Cubedo
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Martin-Yuste
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Sabate
authors.affiliation: Cardiovascular Research Center (CSIC-ICCC), IIB SantPau, c/Sant Antoni Mª Claret 167, 08025 Barcelona, Spain Cardiovascular Research Chair UAB, Barcelona, Spain lbadimon@csic-iccc.org.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000704:Analysis of Variance; D001792:Blood Platelets / Q000473:pathology; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D062645:Percutaneous Coronary Intervention; D010974:Platelet Aggregation / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D051304:Profilins / Q000378:metabolism*; D017131:Thrombectomy / Q000379:methods; D013917:Thrombin / Q000502:physiology; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D061665:Time-to-Treatment
chemical_list: D010975:Platelet Aggregation Inhibitors; D051304:Profilins; D005340:Fibrinogen; D000077144:Clopidogrel; D013917:Thrombin; D013988:Ticlopidine
keywords: Occlusive thrombus ageing; PCI; Platelets; Profilin-1