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 (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.