Document Detail


Molecular imaging of activated matrix metalloproteinases in vascular remodeling.
MedLine Citation:
PMID:  18936327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Matrix metalloproteinase (MMP) activation plays a key role in vascular remodeling. RP782 is a novel indium (111)In-labeled tracer with specificity for activated MMPs. We hypothesized that RP782 can detect injury-induced vascular remodeling in vivo.
METHODS AND RESULTS: Left common carotid artery injury was induced with a guidewire in apolipoprotein E(-/-) mice. Sham surgery was performed on the contralateral artery, which served as control for imaging experiments. Carotid wire injury led to significant hyperplasia and expansive remodeling over a period of 4 weeks. MMP activity, detected by in situ zymography, increased in response to injury and was maximal by 3 to 4 weeks after injury. RP782 (11.1 MBq) was injected intravenously into apolipoprotein E(-/-) mice at 1, 2, 3, and 4 weeks after left carotid injury. MicroSPECT imaging was performed at 2 hours and was followed by CT angiography to localize the carotid arteries. In vivo images revealed focal uptake of RP782 in the injured carotid artery at 2, 3, and 4 weeks. Increased tracer uptake in the injured artery was confirmed by quantitative autoradiography. Pretreatment with 50-fold excess nonlabeled tracer significantly reduced RP782 uptake in injured carotids, thus demonstrating uptake specificity. Weekly changes in the vessel-wall area closely paralleled and correlated with RP782 uptake (Spearman r=0.95, P=0.001).
CONCLUSIONS: Injury-induced MMP activation in the vessel wall can be detected by RP782 microSPECT/CT imaging in vivo. RP782 uptake tracks the hyperplastic process in vascular remodeling and provides an opportunity to track the remodeling process in vivo.
Authors:
Jiasheng Zhang; Lei Nie; Mahmoud Razavian; Masood Ahmed; Lawrence W Dobrucki; Abolfazl Asadi; D Scott Edwards; Michael Azure; Albert J Sinusas; Mehran M Sadeghi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2008-10-20
Journal Detail:
Title:  Circulation     Volume:  118     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-04     Completed Date:  2008-11-26     Revised Date:  2012-06-26    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1953-60     Citation Subset:  AIM; IM    
Affiliation:
Raymond and Beverly Sackler Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn., USA.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Balloon / adverse effects
Animals
Apolipoproteins E / genetics
Autoradiography
Carotid Artery Injuries / metabolism,  pathology,  radionuclide imaging*
Carotid Artery, Common / enzymology*,  pathology,  radionuclide imaging*
Disease Models, Animal
Female
Fluorescent Antibody Technique
Indium / diagnostic use
Matrix Metalloproteinase 2 / metabolism*
Matrix Metalloproteinase 9 / metabolism*
Mice
Mice, Mutant Strains
Sensitivity and Specificity
Tomography, Emission-Computed, Single-Photon / methods*
Grant Support
ID/Acronym/Agency:
HL070295/HL/NHLBI NIH HHS; P01 HL070295-06/HL/NHLBI NIH HHS; R01 HL085093/HL/NHLBI NIH HHS; R01 HL085093/HL/NHLBI NIH HHS; R01 HL085093-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins E; 7440-74-6/Indium; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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