Objectives—Based on previous observations on apolipoprotein(a), apo(a), in human unstable carotid plaques, we explored
whether in the inflammatory environment of human atheroma, proteolytic events affect other hepatic and topically
generated proteins in relation to the issue of plaque stability.
Methods and Results—Forty unstable and 24 stable plaques from endarterectomy segments of affected human carotid
arteries were extracted with buffered saline (PBS) and then 6 mol/L guanidine-hydrochloride (GdHCl) to identify
loosely and tightly bound products, respectively. The extracts were studied before and after ultracentrifugation at d 1.21
g/mL. In the extracts, the concentrations of interleukin (IL)-6, -8, and -18 were significantly higher in the unstable
plaques and correlated to those of MMP-2 and MMP-9. By Western blots, both apoB and apo(a) were highly fragmented
and mostly present in the d 1.21 bottom that also contained fragments of apoE (10 and 22 kDa), decorin, biglycan, and
versican. Fragmentation was higher in the unstable plaques. In baseline plasmas, concentrations of lipids, lipoproteins,
and ILs did not differ between patients with unstable and stable plaques.
Conclusions—In unstable and to a lesser extent in stable plaques, there is a proinflammatory and proteolytic
microenvironment with the generation of fragments with potential pathobiological significance that requires
investigation