TY - JOUR
T1 - In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity
AU - Krams, Rob
AU - Verheye, Stefan
AU - Van Damme, Luc C.A.
AU - Tempel, Dennie
AU - Gourabi, Babak Mousavi
AU - Boersma, Eric
AU - Kockx, Mark M.
AU - Knaapen, Michiel W.M.
AU - Strijder, Chaylendra
AU - Van Langenhove, Glenn
AU - Pasterkamp, Gerard
AU - Van Der Steen, Anton F.W.
AU - Serruys, Patrick W.
PY - 2005/10
Y1 - 2005/10
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 (MΦ) cell densities (%); a vulnerability index (VI) was calculated as VI = MΦ + 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°C (P < 0.05 vs. reference) and 10 cold regions with 0.07 ± 0.03°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 (MΦ) cell densities (%); a vulnerability index (VI) was calculated as VI = MΦ + 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°C (P < 0.05 vs. reference) and 10 cold regions with 0.07 ± 0.03°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 - Inflammation
KW - Intravascular thermography
KW - Macrophages
KW - Metalloproteinases
UR - https://www.scopus.com/pages/publications/26044460514
U2 - 10.1093/eurheartj/ehi461
DO - 10.1093/eurheartj/ehi461
M3 - Article
C2 - 16144779
AN - SCOPUS:26044460514
SN - 0195-668X
VL - 26
SP - 2200
EP - 2205
JO - European Heart Journal
JF - European Heart Journal
IS - 20
ER -