European Heart Journal Advance Access originally published online on September 5, 2005
European Heart Journal 2005 26(20):2200-2205; doi:10.1093/eurheartj/ehi461
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In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity
1Cardiology, Erasmus Medical Center Rotterdam, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands
2Middelheim Hospital, Antwerp, Belgium
3Experimental Cardiology, Utrecht Medical Center, The Netherlands
Received 29 June 2004; revised 24 May 2005; accepted 22 July 2005; online publish-ahead-of-print 5 September 2005.
* Corresponding author. Tel: +31 10 40 87308; fax: +31 10 40 89494. E-mail address: r.krams{at}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 (M
) cell densities (%); a vulnerability index (VI) was calculated as VI=M+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.
Key Words: Macrophages • Intravascular thermography • Inflammation • Metalloproteinases
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