In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity.
OBJECTIVE
Plaque rupture has been associated with a high matrix metalloproteinase (MMP) activity. Recently, regional temperature variations have been observed in atherosclerotic plaques in vivo and ascribed to the presence of macrophages. As macrophages are a major source of MMPs, we examined whether regional temperature changes are related to local MMP activity and macrophage accumulation.


RESULTS
Plaques were experimentally induced in rabbit (n=11) aortas, and at the day of sacrifice, a pull-back was performed with a thermography catheter. Hot (n=10), cold (n=10), and reference (n=11) regions were dissected and analysed for smooth muscle cell (SMC), lipids (L), collagen (COL), and macrophage (MPhi) cell densities (%); a vulnerability index (VI) was calculated as VI=MPhi+L/(SMC+COL). In addition, accumulation and activity of MMP-2 and MMP-9 were determined with zymography. Ten hot regions were identified with an average temperature of 0.40+/-0.03 degrees C (P<0.05 vs. reference) and 10 cold regions with 0.07+/-0.03 degrees C (P<0.05 vs. hot). In the hot regions, a higher macrophage density (173%), less SMC density (77%), and a higher VI (100%) were identified. In addition, MMP-9 (673%) activity was increased. A detailed regression analysis revealed that MMP-9 predicted hot regions better than macrophage accumulation alone.


CONCLUSIONS
In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.
Krams
Rob
R
Cardiology, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. r.krams@erasmusmc.nl
Verheye
Stefan
S
van Damme
Luc C A
LC
Tempel
Dennie
D
Mousavi Gourabi
Babak
B
Boersma
Eric
E
Kockx
Mark M
MM
Knaapen
Michiel W M
MW
Strijder
Chaylendra
C
van Langenhove
Glenn
G
Pasterkamp
Gerard
G
van der Steen
Anton F W
AF
Serruys
Patrick W
PW
D000818:Animals; D001011:Aorta / Q000201:enzymology; D050197:Atherosclerosis / Q000201:enzymology / Q000473:pathology; D003080:Cold Temperature; D006358:Hot Temperature; D008264:Macrophages / Q000201:enzymology* / Q000502:physiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000473:pathology; D011817:Rabbits; D013817:Thermography
D020780:Matrix Metalloproteinase 9