on October 30, 2003
Published online before print October 30, 2003, doi: 10.1161/01.ATV.0000104013.71118.53
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Submitted on September 16, 2003
Accepted on October 17, 2003
Evidence for a Proinflammatory and Proteolytic Environment in Plaques From Endarterectomy Segments of Human Carotid Arteries
Marilena Formato ;
From the Department of Medicine (M. Farina, C.E.) and Department of Medicine and Department of Biochemistry and Molecular Biology (A.M.S.), University of Chicago, Ill; Dipartimento di Scienze Fisiologiche, Biochimiche e Cellulari, University of Sassari (M. Formato, G.M.C.), Italy; Centro Cardiologico Monzino (R.S., A.G., P.B.) and Dipartimento di Patologia (M.M.), University of Milan, Italy.
* To whom correspondence should be addressed. E-mail: ascanu{at}medicine.bsd.uchicago.edu.
Objectives--Based on previous observations on apolipoprotein(a), aoo(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.
Key words: Stable and unstable carotid plaques • apolipoproteins • interleukins • metalloproteinases • proteoglycans
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