CHARACTERIZATION OF THE RELATIVE THROMBOGENICITY OF ATHEROSCLEROTIC PLAQUE COMPONENTS - IMPLICATIONS FOR CONSEQUENCES OF PLAQUE RUPTURE

Objectives. The purpose of this study was to determine whether differe nt components of human atherosclerotic plaques exposed to flowing bloo d resulted in different degrees of thrombus formation. Background. It is likely that the nature of the substrate exposed after spontaneous o r angioplasty induced plaque rupture is one factor determining whether an unstable plaque proceeds rapidly to an occlusive thrombus or persi sts 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 re lative thrombogenicity of different components of human atheroscleroti c plaques is not well established. Methods. We investigated thrombus f ormation on foam cell rich matrix (obtained from fatty streaks), colla gen-rich matrix (from sclerotic plaques), collagen poor matrix without cholesterol crystals (from fibrolipid plaques), atheromatous core wit h abundant cholesterol crystals (from atheromatous plaques) and segmen ts of normal intima derived from human aortas at necropsy. Specimens w ere mounted in a tubular chamber placed within an ex vivo extracorpore al 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 quant itated by measurement of indium-labeled platelets and morphometric ana lysis. Under similar conditions, substrates were perfused with heparin ized human blood (2 IU/ml) in an in vitro system, and thrombus formati on was similarly evaluated. Results. Thrombus formation on atheromatou s core was up to sixfold greater than that on other substrates, includ ing collagen rich matrix (p = 0.0001) in both heterologous and homolog ous systems. Although the atheromatous core had a more irregular expos ed surface and thrombus formation tended to increase with increasing r oughness, the atheromatous core remained the most thrombogenic substra te when the substrates were normalized by the degree of irregularity a s defined by the roughness index (p 0.002). Conclusions. The atheromat ous core is the most thrombogenic component of human atherosclerotic p laques. 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 thrombogenici ty of their content.