UNLABELLED: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques and play an important role in plaque instability. METHODS: Using (99m)Tc-labeled broad-spectrum MMP inhibitor (MPI), we performed noninvasive imaging of MMP expression with micro-SPECT/micro-CT in mice deficient in apolipoprotein E (ApoE(-/-), n = 14), mice deficient in low-density-lipoprotein receptor (LDLR(-/-), n = 14), and C57/BL6 mice as controls (n = 7). Seven ApoE(-/-) and 7 LDLR(-/-) received a high-cholesterol diet. After in vivo imaging, aortas were explanted, ex vivo images acquired, and the percent injected dose of MPI per gram (%ID/g) determined, followed by histologic characterization of atherosclerotic lesions. RESULTS: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT, with confirmation by micro-CT of anatomic location and aortic calcification. %ID/g in each part of the aorta was highest in ApoE(-/-) that were fed a high-cholesterol diet, followed by LDLR(-/-) that were fed a high-cholesterol diet, ApoE(-/-) that were fed normal chow, and LDLR(-/-) that were fed normal chow. The control mice had minimal MPI uptake. A significant correlation was noted between %ID/g and % area positive for macrophages (r = 0.81, P = 0.009), MMP-2 (r = 0.65, P = 0.013), and MMP-9 (r = 0.62, P = 0.008). CONCLUSION: This study demonstrates the usefulness of molecular imaging for noninvasive assessment of the extent of MMP expression in various transgenic mouse models of atherosclerosis receiving a normal or hyperlipidemic diet. It is conceivable that such a strategy may be translationally developed for identification of unstable atherosclerotic plaques.
UNLABELLED: Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques and play an important role in plaque instability. METHODS: Using (99m)Tc-labeled broad-spectrum MMP inhibitor (MPI), we performed noninvasive imaging of MMP expression with micro-SPECT/micro-CT in mice deficient in apolipoprotein E (ApoE(-/-), n = 14), mice deficient in low-density-lipoprotein receptor (LDLR(-/-), n = 14), and C57/BL6 mice as controls (n = 7). Seven ApoE(-/-) and 7 LDLR(-/-) received a high-cholesterol diet. After in vivo imaging, aortas were explanted, ex vivo images acquired, and the percent injected dose of MPI per gram (%ID/g) determined, followed by histologic characterization of atherosclerotic lesions. RESULTS: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT, with confirmation by micro-CT of anatomic location and aortic calcification. %ID/g in each part of the aorta was highest in ApoE(-/-) that were fed a high-cholesterol diet, followed by LDLR(-/-) that were fed a high-cholesterol diet, ApoE(-/-) that were fed normal chow, and LDLR(-/-) that were fed normal chow. The control mice had minimal MPI uptake. A significant correlation was noted between %ID/g and % area positive for macrophages (r = 0.81, P = 0.009), MMP-2 (r = 0.65, P = 0.013), and MMP-9 (r = 0.62, P = 0.008). CONCLUSION: This study demonstrates the usefulness of molecular imaging for noninvasive assessment of the extent of MMP expression in various transgenic mouse models of atherosclerosis receiving a normal or hyperlipidemic diet. It is conceivable that such a strategy may be translationally developed for identification of unstable atherosclerotic plaques.
Authors: Dayuan Li; Amit R Patel; Alexander L Klibanov; Christopher M Kramer; Mirta Ruiz; Bum-Yong Kang; Jawahar L Mehta; George A Beller; David K Glover; Craig H Meyer Journal: Circ Cardiovasc Imaging Date: 2010-05-04 Impact factor: 7.792
Authors: Emilia S Olson; Michael A Whitney; Beth Friedman; Todd A Aguilera; Jessica L Crisp; Fred M Baik; Tao Jiang; Stephen M Baird; Sotirios Tsimikas; Roger Y Tsien; Quyen T Nguyen Journal: Integr Biol (Camb) Date: 2012-04-26 Impact factor: 2.192
Authors: Ryan S Lim; Jeffrey L Suhalim; Shinobu Miyazaki-Anzai; Makoto Miyazaki; Moshe Levi; Eric O Potma; Bruce J Tromberg Journal: J Lipid Res Date: 2011-09-23 Impact factor: 5.922