Matrix Metalloproteinase Activation Predicts Amelioration of Remodeling After Dietary Modification in Injured Arteries
Overview
Authors
Affiliations
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.
Methods And 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 One week after surgery, a group of animals were withdrawn from the high-fat diet.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.
Buchler A, Munch M, Farber G, Zhao X, Al-Haddad R, Farber E Mol Imaging Biol. 2021; 24(1):93-103.
PMID: 34231104 DOI: 10.1007/s11307-021-01626-9.
Molecular Imaging Using Cardiac PET/CT: Opportunities to Harmonize Diagnosis and Therapy.
Thackeray J Curr Cardiol Rep. 2021; 23(8):96.
PMID: 34196821 PMC: 8249297. DOI: 10.1007/s11886-021-01526-y.
Perspectives on Small Animal Radionuclide Imaging; Considerations and Advances in Atherosclerosis.
Meester E, Krenning B, de Swart J, Segbers M, Barrett H, Bernsen M Front Med (Lausanne). 2019; 6:39.
PMID: 30915335 PMC: 6421263. DOI: 10.3389/fmed.2019.00039.
Role of PET/CT in the Evaluation of Aortic Disease.
Kim J, Song H Chonnam Med J. 2018; 54(3):143-152.
PMID: 30288369 PMC: 6165921. DOI: 10.4068/cmj.2018.54.3.143.
Novel Arginine-containing Macrocyclic MMP Inhibitors: Synthesis, Tc-labeling, and Evaluation.
Ye Y, Toczek J, Gona K, Kim H, Han J, Razavian M Sci Rep. 2018; 8(1):11647.
PMID: 30076321 PMC: 6076275. DOI: 10.1038/s41598-018-29941-2.