Assessment of Novel Antioxidant Therapy in Atherosclerosis by Contrast Ultrasound Molecular Imaging

Tamara (Tami) Atkinson, William Packwood, Aris Xie, Sherry Liang, Qi Yue, Zaverio Ruggeri, Jose Lopez, Brian P. Davidson, Jonathan Lindner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Ultrasound molecular imaging was used to evaluate the therapeutic effects of antioxidant therapy with EUK-207, which has superoxide dismutase and catalase activities, on suppressing high-risk atherosclerotic features. Methods: Mice with age-dependent atherosclerosis produced by deletion of the low-density lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207 or vehicle was administered for the preceding 8 weeks. Therapy for 28 weeks was also studied for 40-week-old mice. Ultrasound molecular imaging of the thoracic aorta was performed with contrast agents targeted to endothelial P-selectin, von Willebrand factor A1-domain, and platelet glycoprotein Ibα or control agent. Aortic plaque area and macrophage content were assessed by histology. Results: In 20-week-old double-knockout mice, EUK-207 compared with sham therapy produced only nonsignificant trends for reduction in molecular imaging signal for endothelial P-selectin, von Willebrand factor A1-domain, and platelet adhesion. At 40 weeks, EUK-207 given for 8 or 28 weeks significantly (P <.05) reduced signal for all three endothelial-associated events essentially to background levels, with the exception of glycoprotein Ibα signal after 8 weeks (P =.06). On aortic histology, EUK-207 therapy for 8 weeks did not affect plaque area or macrophage content at either age. However, EUK-207 for 28 weeks almost completely suppressed plaque development (350 ± 258 vs 4 ± 6 × 103 μm2, P =.014) and macrophage content (136 ± 103 vs 3 ± 2 × 103 μm2, P =.002) compared with control mice at 40 weeks. Conclusions: Molecular imaging can be used to assess vascular responses to antioxidants and has demonstrated that certain antioxidants reduce vascular endothelial activation and platelet adhesion, but reductions in plaque size and macrophage content occurs only with long-duration therapy that is started early.

Original languageEnglish (US)
Pages (from-to)1252-1259.e1
JournalJournal of the American Society of Echocardiography
Volume31
Issue number11
DOIs
StatePublished - Nov 1 2018

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Molecular Imaging
Ultrasonography
Atherosclerosis
Antioxidants
Macrophages
Platelet Glycoprotein GPIb-IX Complex
P-Selectin
von Willebrand Factor
Blood Vessels
Histology
Therapeutics
Platelet Membrane Glycoproteins
LDL Receptors
Platelet Activation
Therapeutic Uses
Thoracic Aorta
Knockout Mice
Catalase
Contrast Media
Superoxide Dismutase

Keywords

  • Antioxidants
  • Atherosclerosis
  • Contrast ultrasound
  • Platelets
  • Reactive oxygen species

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Assessment of Novel Antioxidant Therapy in Atherosclerosis by Contrast Ultrasound Molecular Imaging. / Atkinson, Tamara (Tami); Packwood, William; Xie, Aris; Liang, Sherry; Yue, Qi; Ruggeri, Zaverio; Lopez, Jose; Davidson, Brian P.; Lindner, Jonathan.

In: Journal of the American Society of Echocardiography, Vol. 31, No. 11, 01.11.2018, p. 1252-1259.e1.

Research output: Contribution to journalArticle

Atkinson, Tamara (Tami) ; Packwood, William ; Xie, Aris ; Liang, Sherry ; Yue, Qi ; Ruggeri, Zaverio ; Lopez, Jose ; Davidson, Brian P. ; Lindner, Jonathan. / Assessment of Novel Antioxidant Therapy in Atherosclerosis by Contrast Ultrasound Molecular Imaging. In: Journal of the American Society of Echocardiography. 2018 ; Vol. 31, No. 11. pp. 1252-1259.e1.
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AU - Atkinson, Tamara (Tami)

AU - Packwood, William

AU - Xie, Aris

AU - Liang, Sherry

AU - Yue, Qi

AU - Ruggeri, Zaverio

AU - Lopez, Jose

AU - Davidson, Brian P.

AU - Lindner, Jonathan

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N2 - Background: Ultrasound molecular imaging was used to evaluate the therapeutic effects of antioxidant therapy with EUK-207, which has superoxide dismutase and catalase activities, on suppressing high-risk atherosclerotic features. Methods: Mice with age-dependent atherosclerosis produced by deletion of the low-density lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207 or vehicle was administered for the preceding 8 weeks. Therapy for 28 weeks was also studied for 40-week-old mice. Ultrasound molecular imaging of the thoracic aorta was performed with contrast agents targeted to endothelial P-selectin, von Willebrand factor A1-domain, and platelet glycoprotein Ibα or control agent. Aortic plaque area and macrophage content were assessed by histology. Results: In 20-week-old double-knockout mice, EUK-207 compared with sham therapy produced only nonsignificant trends for reduction in molecular imaging signal for endothelial P-selectin, von Willebrand factor A1-domain, and platelet adhesion. At 40 weeks, EUK-207 given for 8 or 28 weeks significantly (P <.05) reduced signal for all three endothelial-associated events essentially to background levels, with the exception of glycoprotein Ibα signal after 8 weeks (P =.06). On aortic histology, EUK-207 therapy for 8 weeks did not affect plaque area or macrophage content at either age. However, EUK-207 for 28 weeks almost completely suppressed plaque development (350 ± 258 vs 4 ± 6 × 103 μm2, P =.014) and macrophage content (136 ± 103 vs 3 ± 2 × 103 μm2, P =.002) compared with control mice at 40 weeks. Conclusions: Molecular imaging can be used to assess vascular responses to antioxidants and has demonstrated that certain antioxidants reduce vascular endothelial activation and platelet adhesion, but reductions in plaque size and macrophage content occurs only with long-duration therapy that is started early.

AB - Background: Ultrasound molecular imaging was used to evaluate the therapeutic effects of antioxidant therapy with EUK-207, which has superoxide dismutase and catalase activities, on suppressing high-risk atherosclerotic features. Methods: Mice with age-dependent atherosclerosis produced by deletion of the low-density lipoprotein receptor and Apobec-1 were studied at 20 and 40 weeks of age. EUK-207 or vehicle was administered for the preceding 8 weeks. Therapy for 28 weeks was also studied for 40-week-old mice. Ultrasound molecular imaging of the thoracic aorta was performed with contrast agents targeted to endothelial P-selectin, von Willebrand factor A1-domain, and platelet glycoprotein Ibα or control agent. Aortic plaque area and macrophage content were assessed by histology. Results: In 20-week-old double-knockout mice, EUK-207 compared with sham therapy produced only nonsignificant trends for reduction in molecular imaging signal for endothelial P-selectin, von Willebrand factor A1-domain, and platelet adhesion. At 40 weeks, EUK-207 given for 8 or 28 weeks significantly (P <.05) reduced signal for all three endothelial-associated events essentially to background levels, with the exception of glycoprotein Ibα signal after 8 weeks (P =.06). On aortic histology, EUK-207 therapy for 8 weeks did not affect plaque area or macrophage content at either age. However, EUK-207 for 28 weeks almost completely suppressed plaque development (350 ± 258 vs 4 ± 6 × 103 μm2, P =.014) and macrophage content (136 ± 103 vs 3 ± 2 × 103 μm2, P =.002) compared with control mice at 40 weeks. Conclusions: Molecular imaging can be used to assess vascular responses to antioxidants and has demonstrated that certain antioxidants reduce vascular endothelial activation and platelet adhesion, but reductions in plaque size and macrophage content occurs only with long-duration therapy that is started early.

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KW - Atherosclerosis

KW - Contrast ultrasound

KW - Platelets

KW - Reactive oxygen species

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