In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity.
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.
|Keywords||*Cold, *Heat, Animals, Aorta/enzymology, Atherosclerosis/enzymology/pathology, Macrophages/*enzymology/physiology, Male, Matrix Metalloproteinase 9/*metabolism, Models, Animal, Muscle, Smooth, Vascular/enzymology/pathology, Myocytes, Smooth Muscle/enzymology/pathology, Rabbits, Thermography|
|Persistent URL||dx.doi.org/10.1093/eurheartj/ehi461, hdl.handle.net/1765/13907|
|Journal||European Heart Journal|
|Note||Epub 2005 Sep 5|
Krams, R, Verheye, S, van Damme, L.C.A, Tempel, D, Mousavi Gourabi, B, Boersma, H, … Serruys, P.W.J.C. (2005). In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity. European Heart Journal, 26(20), 2200–2205. doi:10.1093/eurheartj/ehi461