Abstract
PurposeThe upregulation of vascular cell adhesion molecule-1(VCAM-1) on vascular endothelium plays a great role in the progression of atherosclerosis (AS). In this study, ultrasound molecular imaging was performed to monitor the inflammation injuries in the onset and progression of atherosclerosis with microbubbles targeted to VCAM-1.MethodsMice deficient for the apolipoprotein E (ApoE-/-mice) with high-cholesterol diet were studied as an age-dependent model of atherosclerosis. At 8, 16, 24, and 32 weeks of age, contrast enhanced ultrasound (CEU) molecular imaging of proximal ascending aorta was performed with microbubbles targeted to VCAM-1. Plaque size, monocytes infiltration and the expression of VCAM-1 in the proximal ascending aorta were assessed by histology and western blot analysis, separately.ResultsIn ApoE-/- mice, molecular imaging for VCAM-1 detected selective signal enhancement (P<0.01 versus non-targeted microbubbles) at all ages of ApoE-/- mice. Moreover, signals from targeted microbubbles increased from 8wks to 32wks age (P<0.05 for trend) in ApoE-/- mice, indicating the upregulation of VCAM-1 with the progression of atherosclerosis. Consistent with CEU imaging results, both western blot analysis and immunohistochemistry revealed the expression of VCAM-1 and monocytes infiltration were age-dependent in ApoE-/- mice.ConclusionsCEU molecular imaging can be used to noninvasively detect the VCAM-1 expression on the endothelium in the progression of atherosclerosis. By investigating specific molecular biomarkers, it could help to monitor the inflammation and the progression of AS, which may in some extent contribute to the prediction of vulnerable plaque.
Highlights
It is widely accepted that inflammation plays a key regulatory role in the pathogenesis of atherosclerosis (AS) and its complications [1,2,3]
Signals from targeted microbubbles increased from 8wks to 32wks age (P
Consistent with contrast enhanced ultrasound (CEU) imaging results, both western blot analysis and immunohistochemistry revealed the expression of VCAM-1 and monocytes infiltration were age-dependent in ApoE-/- mice
Summary
It is widely accepted that inflammation plays a key regulatory role in the pathogenesis of atherosclerosis (AS) and its complications [1,2,3]. Among the specific molecular targets for inflammation, vascular cell adhesion molecule-1 (VCAM-1), expressed on activated endothelial cells, is regarded as an ideal target for CEU imaging because there is no or less constitutive expression in normal conditions [10,11,12]. VCAM-1 plays an important role in the onset of AS by recruiting monocytes and lymphocytes to the arterial intima. It participates in the ongoing inflammatory cascade and the complete course of vulnerable plaque development [13,14]. The dynamics process of inflammation and the progression of AS from the initial to the advanced plaque were monitored in vivo
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