Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque
Imran Rashid, Ghassan J Maghzal, Yung-Chih Chen, David Cheng, Jihan Talib, Darren Newington, Minqin Ren, Saumitra K Vajandar, Amy Searle, Ana Maluenda, Eva-Lotte Lindstedt, Andrew Jabbour, Antony J Kettle, Andre Bongers, Carl Power, Erik Michaelsson, Karlheinz Peter, Roland Stocker
European Heart Journal | OXFORD UNIV PRESS | Published : 2018
Aims: As the inflammatory enzyme myeloperoxidase (MPO) is abundant in ruptured human atherosclerotic plaques, we aimed to investigate the role of MPO as a potential diagnostic and therapeutic target for high-risk plaque. Methods and results: We employed the tandem stenosis model of atherosclerotic plaque instability in apolipoprotein E gene knockout (Apoe-/-) mice. To test the role of MPO, we used Mpo-/-Apoe-/- mice and the 2-thioxanthine MPO inhibitor AZM198. In vivo MPO activity was assessed by liquid chromatography-tandem mass spectrometry detection of 2-chloroethidium generation from hydroethidine and by bis-5HT-DTPA-Gd (MPO-Gd) molecular magnetic resonance imaging (MRI), while plaque ph..View full abstract
Awarded by National Health and Medical Research Council (NHMRC) of Australia
Awarded by Australian Research Council
This work was supported by National Health and Medical Research Council (NHMRC) of Australia [1060804 to R.S. and A.J.K., Program 1052616 to R.S.], the Australian Research Council [Discovery Project 170101453 to R.S.], and a St Vincent's Clinic Foundation to R.S., I.R., and A.J. Y.C.C. was supported by a fellowship of the National Heart Foundation of Australia. K.P. and R.S. are supported by NHMRC Fellowships. We also acknowledge infrastructure support from New South Wales Health, the Victorian State Government and the Australian National Imaging Facility.