Inflammation in Atherosclerosis

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Abstract
Background— Matrix metalloproteinases (MMPs) in inflamed atherosclerotic plaques may contribute to extracellular matrix remodeling and the onset of acute thrombotic complications. Methods and Results— To test the hypothesis that optical molecular imaging with the use of an activatable near-infrared fluorescence (NIRF) probe can detect enzymatic action of MMP in atherosclerotic plaques, we used a NIRF substrate for gelatinases (MMP-2/gelatinase-A and MMP-9/gelatinase-B) in apolipoprotein E–deficient (apoE−/−) mice that consumed a high-cholesterol diet for 12 weeks and age-matched apoE+/+ mice as control. The aortas of apoE−/− mice at 24 hours after probe yielded intense NIRF signals, as detected by NIRF reflectance ex vivo, compared with negligible signals in aortas of apoE+/+ mice with/without probe administration or atherosclerotic apoE−/− aortas without probe. Gelatinase inhibitor treatment abolished NIRF signals in apoE−/− mouse aortas ex vivo. Sites of gelatinase activity visualized by NIRF colocalize...