In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity
Rob Krams1, Stefan Verheye, Luc C A van Damme
1Cardiology, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands. r.krams@erasmusmc.nl
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.
Insights
Regional temperature variations in atherosclerotic plaques correlate with increased matrix metalloproteinase-9 (MMP-9) activity and macrophage accumulation. In vivo thermography can identify vulnerable plaques with higher MMP-9 levels.
Area of Science:
- Cardiovascular Research
- Atherosclerosis Pathophysiology
- Biomedical Imaging
Background:
- Plaque rupture is linked to high matrix metalloproteinase (MMP) activity.
- Macrophages in atherosclerotic plaques cause regional temperature variations.
- Macrophages are a primary source of MMPs.
Purpose of the Study:
- To investigate the relationship between regional temperature changes in atherosclerotic plaques and local matrix metalloproteinase (MMP) activity and macrophage accumulation.
- To determine if in vivo temperature variations can serve as a marker for plaque vulnerability.
Main Methods:
- Experimental induction of plaques in rabbit aortas.
- In vivo thermography catheter pull-back to identify hot and cold plaque regions.
- Dissection and analysis of plaque regions for smooth muscle cell (SMC), lipid (L), collagen (COL), and macrophage (MPhi) densities.
- Calculation of a vulnerability index (VI).
- Zymography to determine MMP-2 and MMP-9 accumulation and activity.
Main Results:
- Hot plaque regions showed significantly higher temperatures compared to reference and cold regions.
- Hot regions exhibited increased macrophage density (173%), decreased SMC density (77%), and a higher vulnerability index (100%).
- Matrix metalloproteinase-9 (MMP-9) activity was significantly elevated (673%) in hot regions.
- MMP-9 activity was a stronger predictor of hot regions than macrophage accumulation alone.
Conclusions:
- In vivo temperature measurements can effectively detect atherosclerotic plaques with higher macrophage content.
- Thermography can identify plaques characterized by reduced smooth muscle cell density and increased MMP-9 activity.
- Regional plaque temperature variations are a valuable indicator of underlying pathological processes, including elevated MMP-9 activity.
