Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.
OBJECTIVE
To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification.


RESULTS
Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a (99m)Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery.


CONCLUSIONS
MMP activation predicts the progression of vascular remodeling and can track the effect of dietary modification after vascular injury.
Veterans Affairs, Connecticut Healthcare System, West Haven, CT 06516, USA.
Sina
S
Tavakoli
Mahmoud
M
Razavian
Jiasheng
J
Zhang
Lei
L
Nie
Ravi
R
Marfatia
Lawrence W
LW
Dobrucki
Albert J
AJ
Sinusas
Simon
S
Robinson
D Scott
DS
Edwards
Mehran M
MM
Sadeghi
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D020212:Carotid Artery Injuries / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D017536:Carotid Artery, Common / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005260:Female; D007249:Inflammation / Q000201:enzymology / Q000209:etiology; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging; D011480:Protease Inhibitors / Q000494:pharmacology; D013997:Time Factors; D015899:Tomography, Emission-Computed, Single-Photon; D055114:X-Ray Microtomography
D001057:Apolipoproteins E; D004041:Dietary Fats; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D020782:Matrix Metalloproteinases