title: Early onset of endothelial cell proliferation in coronary thrombi of patients with an acute myocardial infarction: implications for plaque healing.
abstract: OBJECTIVE
  Coronary thrombotic occlusion in ST-segment elevation myocardial infarction (STEMI) patients is often preceded by episodes of progressive growth of the thrombus mass. Similar to wound healing, the organization of thrombus could depend on ingrowth of microvessels in order to stabilize its structure. We investigated the patterns of neovascularization in different stages of coronary thrombus evolution.
  
  
  METHODS
  Thrombectomy materials obtained from STEMI patients were histologically classified according to thrombus age in three groups: fresh (< 1 day), lytic (1-5 days) or organized (> 5 days) thrombi. Forty thrombi of each group were randomly collected. Neovascularization in the thrombi was evaluated histomorphologically and with immunodouble stains to visualize various differentiation antigens of endothelial cells (ECs) and primitive cells.
  
  
  RESULTS
  Morphologically, ECs in the coronary thrombi manifested as: single cells, cell clusters or microvessels. CD31+/CD34+ ECs were present in 98% of all the thrombi. In addition, endothelial clusters were found in 63% of the fresh thrombi (< 1 day). CD105+, Ki67+, or C-kit+ ECs (active, proliferating cells) were observed in all the stages, but significantly more in organized thrombi (> 5 days) compared with fresh and lytic ones (< 5 days), and mainly as cell clusters (P ≤ 0.05 for all). CD133+ primitive cells were found only sporadically in 11% of all the samples.
  
  
  CONCLUSIONS
  EC proliferation is initiated very early, and gradually progresses during the organization process of thrombus after coronary plaque disruption, with only a limited contribution of primitive cells in this process.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: M C
authors.initials: MC
authors.lastname: Kramer
authors.forename: C M
authors.initials: CM
authors.lastname: VAN DER Loos
authors.forename: H J P
authors.initials: HJ
authors.lastname: Ploegmakers
authors.forename: O J
authors.initials: OJ
authors.lastname: DE Boer
authors.forename: K T
authors.initials: KT
authors.lastname: Koch
authors.forename: J G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: R J
authors.initials: RJ
authors.lastname: DE Winter
authors.forename: A C
authors.initials: AC
authors.lastname: VAN DER Wal
mesh_terms: D000071916:AC133 Antigen; D000368:Aged; D000704:Analysis of Variance; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D003328:Coronary Thrombosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D003331:Coronary Vessels / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D000071063:Endoglin; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000032:analysis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis; D017131:Thrombectomy
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015415:Biomarkers; C064206:ENG protein, human; D000071063:Endoglin; D006023:Glycoproteins; D019394:Ki-67 Antigen; C000606023:PROM1 protein, human; D010455:Peptides; D011956:Receptors, Cell Surface; D019009:Proto-Oncogene Proteins c-kit