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Contrast Ultrasound Imaging of the Aorta Does Not Affect Progression of Atherosclerosis or Cardiovascular Biomarkers in ApoE-/- Mice.

ABSTRACT: Ultrasound contrast agents (UCAs) enhance cardiovascular ultrasound imaging. Adverse biological effects have occurred after administration of UCAs, and more research is needed for a comprehensive understanding of the risks involved. We used the ApoE(-/-) mouse model of atherosclerosis to characterize the effects of ultrasound and UCAs on atherosclerosis and plasma biomarkers.Male ApoE(-/-) mice (8 weeks old; n = 24) were intravenously infused with a UCA (2 × 10(10) Definity microbubbles per hour; Lantheus Medical Imaging, North Billerica, MA) and exposed to 2.8-MHz center frequency ultrasound (10 Hz pulse repetition frequency, 1.4 microseconds pulse duration, 2 minutes exposure duration, and 2 sites) at 1 of 3 derated peak rarefactional pressure amplitudes (0, 1.9, or 3.8 MPa), and then consumed either a chow or Western diet for 4 weeks (n = 4 per group). Blood plasma samples were collected before ultrasound exposure and at 2 and 4 weeks after exposure and assayed for total cholesterol and von Willebrand Factor (vWF). A pathologist measured atheroma thickness in formalin-fixed, hematoxylin-eosin-stained transverse aorta sections and scored them for severity of atherosclerosis.Plasma total cholesterol initially averaged 286 mg/dL in the Western diet group and increased to 861 mg/dL after 4 weeks on the diet (P < .0001). Total cholesterol did not increase significantly in the chow diet group. Plasma vWF increased after 2 weeks on the Western diet (P < .0001). Atheroma thickness was greater in animals consuming the Western diet than in chow-fed animals (P < .05). Ultrasound had no significant effect on plasma total cholesterol, plasma vWF, or atheroma thickness.Contrast ultrasound did not increase the severity of atherosclerosis or alter cardiovascular biomarkers in the ApoE(-/-) mouse model.

SUBMITTER: Smith BW

PROVIDER: S-EPMC4471945 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Contrast Ultrasound Imaging of the Aorta Does Not Affect Progression of Atherosclerosis or Cardiovascular Biomarkers in ApoE-/- Mice.

Smith Brendon W BW Simpson Douglas G DG Sarwate Sandhya S Miller Rita J RJ Erdman John W JW O'Brien William D WD

Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine 20150601 6

<h4>Objectives</h4>Ultrasound contrast agents (UCAs) enhance cardiovascular ultrasound imaging. Adverse biological effects have occurred after administration of UCAs, and more research is needed for a comprehensive understanding of the risks involved. We used the ApoE(-/-) mouse model of atherosclerosis to characterize the effects of ultrasound and UCAs on atherosclerosis and plasma biomarkers.<h4>Methods</h4>Male ApoE(-/-) mice (8 weeks old; n = 24) were intravenously infused with a UCA (2 × 10 ...[more]

PMID: 26014332

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Project description:Platelet-endothelial interactions have been linked to increased inflammatory activation and a prothrombotic state in atherosclerosis. The interaction between von Willebrand factor (vWF)-A1 domain and platelet glycoprotein (GP) Ib/IX plays a significant role in mediating the adhesion of platelets to the injured endothelium. In the present study, contrast-enhanced ultrasound (CEU) molecular imaging with microbubbles bearing the vWF-A1 domain was performed to non-invasively monitor activated platelets on the vascular endothelium in the procession of atherosclerosis. A targeted CEU contrast agent was prepared by attaching the vWF-A1 domain to the shell of microbubbles (MbA1). Rat isotype control antibody was used to produce control (Mbctrl) microbubbles. The binding of MbA1 and Mbctrl to activated platelets was assessed in in vitro flow chamber experiments. Apolipoprotein E (ApoE-/-) deficient mice were studied as a model of atherosclerosis. At 8, 16 and 32 weeks of age, CEU molecular imaging of the proximal aorta with MbA1 and Mbctrl was performed and the imaging signals from microbubbles were quantified. Atherosclerotic lesion severity and platelets on the endothelial surface were assessed by histology and immunohistochemistry. In in vitro flow chamber studies, attachment of MbA1 to activated platelets on culture dishes was significantly greater than that of Mbctrl across a range of shear stresses (P<0.05). The attachment of Mbctrl was sparse and not related to the aggregated platelets. As lesion development progressed in the ApoE-/- mice, molecular imaging of activated platelets demonstrated selective signal enhancement of MbA1 (P<0.05 vs. Mbctrl) at all ages. Selective signal enhancement from MbA1 increased from 8 to 32 weeks of age. Immunohistochemistry for GPIIb revealed the presence of platelets on the endothelial cell surface in each group of ApoE-/- mice and that the degree of platelet deposits was age-dependent. The results of the present study indicated that non-invasive CEU molecular imaging with targeted microbubbles bearing the vWF-A1 domain could not only detect activated platelets on the vascular endothelium but also indicate lesion severity in atherosclerosis.

Project description:BACKGROUND:It is still unknown that whether co-existing intracranial stenosis and extracranial carotid vulnerable plaques have higher predictive value for subsequent vascular events. This study aimed to determine the relationship between co-existing extracranial carotid vulnerable plaques and intracranial stenosis and subsequent vascular events utilizing cardiovascular magnetic resonance (CMR) vessel wall imaging. METHODS:Patients who had recent cerebrovascular symptoms in anterior circulation (<?2?weeks) were consecutively enrolled and underwent multi-contrast CMR vessel wall imaging for extracranial carotid arteries and 3D time-of flight CMR angiography for intracranial arteries at baseline. After baseline examination, all patients were followed-up for at least 1?year to determined recurrence of vascular events. The co-existing cerebrovascular atherosclerosis was defined as presence of both intracranial artery stenosis and at least one the following measures of extracranial artery atherosclerosis: plaque, calcification, lipid-rich necrotic core (LRNC), or intraplaque hemorrhage. Univariate and multivariate Cox regressions were used to calculate the hazard ratio (HR) and corresponding 95% confidence interval (CI) of co-existing plaques in predicting subsequent vascular events. RESULTS:In total, 150 patients (mean age: 61.8?±?11.9?years; 109 males) were recruited. During the median follow-up time of 12.1?months, 41 (27.3%) patients experienced vascular events. Co-existing intracranial artery stenosis and extracranial carotid plaque (HR, 3.57; 95% CI, 1.63-7.82; P?=?0.001) and co-existing intracranial artery stenosis and extracranial carotid LRNC (HR, 4.47; 95% CI, 2.15-9.27; P?<?0.001) were significantly associated with subsequent vascular events, respectively. After adjusted for confounding factors and carotid stenosis, these associations remained statistically significant (HR, 5.12; 95% CI, 1.36-19.24; P?=?0.016 and HR, 8.12; 95% CI, 2.41-27.31; P?=?0.001, respectively). CONCLUSIONS:The co-existing cerebrovascular atherosclerotic diseases, particularly co-existing carotid lipid-rich necrotic core and intracranial stenosis, are independent predictors for subsequent vascular events.

Dataset Information

Contrast Ultrasound Imaging of the Aorta Does Not Affect Progression of Atherosclerosis or Cardiovascular Biomarkers in ApoE-/- Mice.

Publications

Contrast Ultrasound Imaging of the Aorta Does Not Affect Progression of Atherosclerosis or Cardiovascular Biomarkers in ApoE-/- Mice.

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