Τίτλος:
Optical imaging of MMP-12 active form in inflammation and aneurysm
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Matrix metalloproteinase (MMP)-12 plays a key role in the development of aneurysm. Like other members of MMP family, MMP-12 is produced as a proenzyme, mainly by macrophages, and undergoes proteolytic activation to generate an active form. Accordingly, molecular imaging of the MMP-12 active form can inform of the pathogenic process in aneurysm. Here, we developed a novel family of fluorescent probes based on a selective MMP-12 inhibitor, RXP470.1 to target the active form of MMP-12. These probes were stable in complex media and retained the high affinity and selectivity of RXP470.1 for MMP-12. Amongst these, probe 3 containing a zwitterionic fluorophore, ZW800-1, combined a favorable affinity profile toward MMP-12 and faster blood clearance. In vivo binding of probe 3 was observed in murine models of sterile inflammation and carotid aneurysm. Binding specificity was demonstrated using a non-binding homolog. Co-immunostaining localized MMP-12 probe binding to MMP-12 positive areas and F4/80 positive macrophages in aneurysm. In conclusion, the active form of MMP-12 can be detected by optical imaging using RXP470.1-based probes. This is a valuable adjunct for pathophysiology research, drug development, and potentially clinical applications.
Συγγραφείς:
Razavian, M.
Bordenave, T.
Georgiadis, D.
Beau, F.
Zhang, J.
Golestani, R.
Toczek, J.
Jung, J.-J.
Ye, Y.
Kim, H.-Y.
Han, J.
Dive, V.
Devel, L.
Sadeghi, M.M.
Περιοδικό:
Scientific Reports
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
differentiation antigen; fluorescent dye; macrophage elastase; matrix metalloproteinase inhibitor; MMP12 protein, human; monocyte-macrophage differentiation antigen; peptide; protein binding; quaternary ammonium derivative; RXP470.1 peptide; sulfonic acid derivative; ZW800-1 compound, aneurysm; animal; C57BL mouse; carotid artery; chemistry; diagnostic imaging; disease model; fluorescence imaging; gene expression; genetics; human; immunology; inflammation; macrophage; metabolism; mouse; pathology; procedures; synthesis, Aneurysm; Animals; Antigens, Differentiation; Carotid Arteries; Disease Models, Animal; Fluorescent Dyes; Gene Expression; Humans; Inflammation; Macrophages; Matrix Metalloproteinase 12; Matrix Metalloproteinase Inhibitors; Mice; Mice, Inbred C57BL; Optical Imaging; Peptides; Protein Binding; Quaternary Ammonium Compounds; Sulfonic Acids
