Mitochondrial uncoupling protein 2 mediates temperature heterogeneity in atherosclerotic plaques.
OBJECTIVE
Rupture-prone atherosclerotic plaques show an elevated temperature, but a molecular explanation for this phenomenon is unknown. Here, we investigated whether mitochondrial uncoupling protein 2 (UCP2) could be involved because this protein is a macrophage homologue of thermogenin in brown fat tissue.


RESULTS
Immunohistochemistry, western blotting, and real-time quantitative polymerase chain reaction were used to detect UCP2 expression in human and rabbit atherosclerotic plaques. Temperature was measured in plaques with thermography catheters and in cultured cells with precision thermometers. UCP2 was abundantly expressed in subendothelial macrophages of atherosclerotic plaques but not in deeper layers of the plaque. Ex vivo temperature measurements in atherosclerotic rabbit thoracic aorta demonstrated a correlation between local plaque temperature, total macrophage mass, and UCP2 expression. In vitro, chemical uncoupling of macrophages with sodium cyanide resulted in heat production (DeltaT = 0.13 +/- 0.04 degrees C vs. controls). Also, overexpression of UCP2 in cultured cells led to a similar increase in temperature.


CONCLUSIONS
Our findings provide evidence that temperature heterogeneity in atherosclerotic plaques is at least in part attributed to UCP2 expression in macrophages. The heat generated might be used to detect unstable, macrophage-rich, atherosclerotic plaques via thermography.
Van De Parre
Tim J L
TJ
Division of Pharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Wilrijk, Belgium.
Martinet
Wim
W
Verheye
Stefan
S
Kockx
Mark M
MM
Van Langenhove
Glenn
G
Herman
Arnold G
AG
De Meyer
Guido R Y
GR
D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D022722:Thermogenesis; D013817:Thermography; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2