title: Characterization of the relative thrombogenicity of atherosclerotic plaque components: implications for consequences of plaque rupture.
abstract: OBJECTIVE
  The purpose of this study was to determine whether different components of human atherosclerotic plaques exposed to flowing blood resulted in different degrees of thrombus formation.
  
  
  BACKGROUND
  It is likely that the nature of the substrate exposed after spontaneous or angioplasty-induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persists as a nonocclusive mural thrombus. Although observational data show that plaque rupture is a potent stimulus for thrombosis, and exposed collagen is suggested to have a predominant role in thrombosis, the relative thrombogenicity of different components of human atherosclerotic plaques is not well established.
  
  
  METHODS
  We investigated thrombus formation on foam cell-rich matrix (obtained from fatty streaks), collagen-rich matrix (from sclerotic plaques), collagen-poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core with abundant cholesterol crystals (from atheromatous plaques) and segments of normal intima derived from human aortas at necropsy. Specimens were mounted in a tubular chamber placed within an ex vivo extracorporeal perfusion system and exposed to heparinized porcine blood (mean [+/- SEM] activated partial thromboplastin time ratio 1.5 +/- 0.04) for 5 min under high shear rate conditions (1,690 s-1). Thrombus was quantitated by measurement of indium-labeled platelets and morphometric analysis. Under similar conditions, substrates were perfused with heparinized human blood (2 IU/ml) in an in vitro system, and thrombus formation was similarly evaluated.
  
  
  RESULTS
  Thrombus formation on atheromatous core was up to sixfold greater than that on other substrates, including collagen-rich matrix (p = 0.0001) in both heterologous and homologous systems. Although the atheromatous core had a more irregular exposed surface and thrombus formation tended to increase with increasing roughness, the atheromatous core remained the most thrombogenic substrate when the substrates were normalized by the degree of irregularity as defined by the roughness index (p = 0.002).
  
  
  CONCLUSIONS
  The atheromatous core is the most thrombogenic component of human atherosclerotic plaques. Therefore, plaques with a large atheromatous core content are at high risk of leading to acute coronary syndromes after spontaneous or mechanically induced rupture because of the increased thrombogenicity of their content.
authors.affiliation: Cardiovascular Biology Laboratory, Massachusetts General Hospital, Boston.
authors.forename: A
authors.initials: A
authors.lastname: Fernández-Ortiz
authors.forename: J J
authors.initials: JJ
authors.lastname: Badimon
authors.forename: E
authors.initials: E
authors.lastname: Falk
authors.forename: V
authors.initials: V
authors.lastname: Fuster
authors.forename: B
authors.initials: B
authors.lastname: Meyer
authors.forename: A
authors.initials: A
authors.lastname: Mailhac
authors.forename: D
authors.initials: D
authors.lastname: Weng
authors.forename: P K
authors.initials: PK
authors.lastname: Shah
authors.forename: L
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D003328:Coronary Thrombosis / Q000209:etiology*; D005487:Foam Cells / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D013552:Swine
chemical_list: D003094:Collagen