TY - JOUR
T1 - In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity
AU - Krams, R.
AU - Verheye, S.
AU - van Damme, L.C.
AU - Tempel, D.
AU - Gourabi, BM
AU - Boersma, E.
AU - Kockx, M.M.
AU - Knaapen, M.W.
AU - Strijder, C.F.
AU - Pasterkamp, G.
AU - van der Steen, A.F.
AU - Serruys, P.W.
PY - 2005
Y1 - 2005
N2 - AIMS: 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.METHODS AND 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.CONCLUSION: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.
AB - AIMS: 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.METHODS AND 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.CONCLUSION: In vivo temperature measurements enable to detect plaques that contain more macrophages, less SMCs, and a higher MMP-9 activity.
KW - Animals
KW - Aorta
KW - Atherosclerosis
KW - Cold Temperature
KW - Hot Temperature
KW - Macrophages
KW - Male
KW - Matrix Metalloproteinase 9
KW - Models, Animal
KW - Muscle, Smooth, Vascular
KW - Myocytes, Smooth Muscle
KW - Rabbits
KW - Thermography
U2 - 10.1093/eurheartj/ehi461
DO - 10.1093/eurheartj/ehi461
M3 - Article
C2 - 16144779
SN - 0195-668X
VL - 26
SP - 2200
EP - 2205
JO - European Heart Journal
JF - European Heart Journal
IS - 20
ER -