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European Heart Journal Advance Access published online on September 5, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi461
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European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received June 29, 2004
Revised May 24, 2005
Accepted July 22, 2005

Preclinical research

In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity

Rob Krams 1*, Stefan Verheye 2, Luc C.A. van Damme 1, Dennie Tempel 1, Babak Mousavi Gourabi 1, Eric Boersma 1, Mark M. Kockx 2, Michiel W.M. Knaapen 2, Chaylendra Strijder 3, Glenn van Langenhove 2, Gerard Pasterkamp 3, Anton F.W. van der Steen 1, and Patrick W. Serruys 1

1 Cardiology, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
2 Middelheim Hospital, Antwerp, Belgium
3 Experimental Cardiology, Utrecht Medical Center, The Netherlands

* To whom correspondence should be addressed.
Rob Krams, E-mail: r.krams{at}erasmusmc.nl


  Abstract

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 (M{Phi}) cell densities (%); a vulnerability index (VI) was calculated as VI = M{Phi} + 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.

Keywords: Macrophages; Intravascular thermography; Inflammation; Metalloproteinases.
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