Evidence for a proinflammatory and proteolytic environment in plaques from endarterectomy segments of human carotid arteries.
OBJECTIVE
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.


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.
Dipartimento di Scienze Fisiologiche, Biochimiche e Cellulari, University of Sassari, Italy.
Marilena
M
Formato
Miriam
M
Farina
Rita
R
Spirito
Marco
M
Maggioni
Anna
A
Guarino
Gian Mario
GM
Cherchi
Paolo
P
Biglioli
Celina
C
Edelstein
Angelo M
AM
Scanu
D000368:Aged; D001053:Apolipoproteins / Q000032:analysis; D015415:Biomarkers; D016893:Carotid Stenosis / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D058575:Decorin; D016894:Endarterectomy, Carotid; D016326:Extracellular Matrix Proteins; D005260:Female; D019791:Guanidine / Q000494:pharmacology; D006801:Humans; D007378:Interleukins / Q000032:analysis; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis; D011506:Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis; D014657:Vasculitis / Q000378:metabolism* / Q000473:pathology
D001053:Apolipoproteins; D015415:Biomarkers; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D007378:Interleukins; D010446:Peptide Fragments; D011506:Proteins; D011509:Proteoglycans; D020782:Matrix Metalloproteinases; D019791:Guanidine