Gelatinolytic activity in atherosclerotic plaques is highly localized and is associated with both macrophages and smooth muscle cells in vivo.
BACKGROUND
Atherosclerosis is considered an inflammatory disease. Recent studies provided evidence for a predominant upstream location of plaque inflammation. The present study introduces a novel technique that evaluates the underlying mechanism of this spatial organization.


RESULTS
In hypercholesterolemic rabbits, atherosclerosis of the infrarenal aorta was induced by a combination of endothelial denudation and a high-cholesterol diet (2% cholesterol for 2 months). At the time of death, aortic vessel segments were dissected and reconstructed with a new technique that preserved the original intravascular ultrasound-derived lumen geometry. This enabled us to study the spatial relation of histological markers like macrophages, smooth muscle cells, lipids, gelatinolytic activity, and oxidized low-density lipoprotein. Results showed a predominant upstream localization of macrophages and gelatinase activity. Colocalization studies indicated that gelatinase activity was associated with macrophages and smooth muscle cells. Further analysis revealed that this was caused by subsets of smooth muscle cells and macrophages, which were associated with oxidized low-density lipoprotein accumulation.


CONCLUSIONS
Upstream localization of a vulnerable plaque phenotype is probably due to an accumulation of oxidized low-density lipoprotein, which activates/induces subsets of smooth muscle cells and macrophages to gelatinase production.
Segers
Dolf
D
Thoraxcenter, Department of Cardiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Helderman
Frank
F
Cheng
Caroline
C
van Damme
Luc C A
LC
Tempel
Dennie
D
Boersma
Eric
E
Serruys
Patrick W
PW
de Crom
Rini
R
van der Steen
Antonius F W
AF
Holvoet
Paul
P
Krams
Rob
R
D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D005780:Gelatin / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology* / Q000473:pathology; D011817:Rabbits
D005780:Gelatin; D018093:Gelatinases