Optical Visualization of Cathepsin K Activity in Atherosclerosis With a Novel, Protease-Activatable Fluorescence Sensor
Farouc A. Jaffer,Dong-Eog Kim,Luisa Quinti,Ching-Hsuan Tung,Elena Aikawa,Ashvin N. Pande,Rainer H. Kohler,Guo-Ping Shi,Peter Libby,Ralph Weissleder +9 more
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TL;DR: Use of this novel protease-activatable NIRF agent for optical imaging in vivo demonstrated preferential localization of enzymatically active CatK to macrophages, consistent with their known greater elastinolytic capabilities compared with smooth muscle cells.
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Abstract: Background— Cathepsin K (CatK), a potent elastinolytic and collagenolytic cysteine protease, likely participates in the evolution and destabilization of atherosclerotic plaques. To assess better the biology of CatK activity in vivo, we developed a novel near-infrared fluorescence (NIRF) probe for imaging of CatK and evaluated it in mouse and human atherosclerosis. Methods and Results— The NIRF imaging agent consists of the CatK peptide substrate GHPGGPQGKC-NH2 linked to an activatable fluorogenic polymer. In vitro, CatK produced a 2- to 14-fold activation of the agent over other cysteine and matrix metalloproteinases (P 8-fold activation over a control imaging agent (P 100% NIRF signal increases in apolipoprotein E−/− mice in vivo (n=13; P<0.05, CatK imaging agent versus control agent) and in human carotid endarterectomy specimens ex vivo (n=14; P<0.05). Fluorescence microscopy of plaque sections demonstrated that enzymatically active Ca...
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References
Compensatory Enlargement of Human Atherosclerotic Coronary Arteries
Seymour Glagov,Elliot Weisenberg,Christopher K. Zarins,Regina Stankunavicius,George J. Kolettis +4 more
TL;DR: It is concluded that human coronary arteries enlarge in relation to plaque area and that functionally important lumen stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area.
3.8K
From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.
Morteza Naghavi,Peter Libby,Erling Falk,S. Ward Casscells,S. Ward Casscells,Silvio H. Litovsky,Silvio H. Litovsky,John A. Rumberger,Juan J. Badimon,Christodoulos Stefanadis,Pedro R. Moreno,Gerard Pasterkamp,Zahi A. Fayad,Peter Stone,Sergio Waxman,Paolo Raggi,Mohammad Madjid,Mohammad Madjid,Alireza Zarrabi,Alireza Zarrabi,Allen P. Burke,Chun Yuan,Peter J. Fitzgerald,David S. Siscovick,Chris L. de Korte,Masanori Aikawa,K.E. Juhani Airaksinen,Gerd Assmann,Christoph R. Becker,James H. Chesebro,Andrew Farb,Zorina S. Galis,Christopher L. Jackson,Ik-Kyung Jang,Wolfgang Koenig,Robert A. Lodder,Keith L. March,Jasenka Demirovic,Mohamad Navab,Silvia G. Priori,Mark D. Rekhter,Raymond D. Bahr,Scott M. Grundy,Roxana Mehran,Antonio Colombo,Eric Boerwinkle,Christie M. Ballantyne,William Insull,Robert S. Schwartz,Robert A. Vogel,Patrick W. Serruys,Göran K. Hansson,David P. Faxon,Sanjay Kaul,Helmut Drexler,Philip Greenland,James E. Muller,Renu Virmani,Renu Virmani,Paul M. Ridker,Douglas P. Zipes,Prediman K. Shah,James T. Willerson,James T. Willerson +63 more
TL;DR: The term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future and a quantitative method for cumulative risk assessment of vulnerable patients needs to be developed.
Shedding light onto live molecular targets
TL;DR: Optical sensing of specific molecular targets and pathways deep inside living mice has become possible as a result of a number of advances, which will provide new tools making it possible to understand more fully the functioning of protein networks, diagnose disease earlier and speed along drug discovery.
2K
In vivo imaging of tumors with protease-activated near-infrared fluorescent probes.
TL;DR: In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters, and this strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity.
1.7K
Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency
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1K