Key result
Contrast-enhanced ultrasound molecular imaging with VCAM-1 targeted microbubbles detected selective signal enhancement compared to non-targeted microbubbles (P<0.01) at all ages in ApoE-/- mice.
Why the study?
Does contrast-enhanced ultrasound molecular imaging with VCAM-1 targeted microbubbles detect and monitor inflammation in the progression of atherosclerosis in an ApoE-/- mouse model?
Does contrast-enhanced ultrasound molecular imaging with VCAM-1 targeted microbubbles detect and monitor inflammation in the progression of atherosclerosis in an ApoE-/- mouse model?
p-value: p=<0.01
Contrast-enhanced ultrasound molecular imaging with VCAM-1 targeted microbubbles can noninvasively detect and monitor endothelial inflammation during the progression of atherosclerosis in a preclinical model.
VCAM-1 targeted imaging may track atherosclerosis progression preclinically; leaves open human translation and validation studies.
PURPOSE: The 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. METHODS: Mice 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. RESULTS: In 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. CONCLUSIONS: CEU 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.
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Sun et al. (2017) studied Atherosclerosis (n=116). VCAM-1 targeted microbubbles (CEU molecular imaging) vs. Non-targeted control microbubbles was evaluated on Selective signal enhancement for VCAM-1 targeted microbubbles (p=<0.01). Contrast-enhanced ultrasound molecular imaging with VCAM-1 targeted microbubbles detected selective signal enhancement compared to non-targeted microbubbles (P<0.01) at all ages in ApoE-/- mice.
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