Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis: Effects of antioxidant therapy with NADPH oxidase inhibition

Yani Liu, Brian P. Davidson, Qi Yue, Todd Belcik, Aris Xie, Yoichi Inaba, Owen McCarty, Garth W. Tormoen, Yan Zhao, Zaverio M. Ruggeri, Beat A. Kaufmann, Jonathan Lindner

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Background-In atherosclerosis, local generation of reactive oxygen species amplifies the inflammatory response and contributes to plaque vulnerability. We used molecular imaging to test whether inhibition of NADPH oxidase with apocynin would reduce endothelial inflammatory activation and endothelial-platelet interactions, thereby interrupting progression to high-risk plaque phenotype. Methods and Results-Mice deficient for both the low-density lipoprotein receptor and Apobec-1 were studied at 30 weeks of age and again after 10 weeks with or without apocynin treatment (10 or 50 mg/kg per day orally). In vivo molecular imaging of vascular cell adhesion molecule-1 (VCAM 1) P-selectin, and platelet glycoprotein-1b (GPIb) in the thoracic aorta was performed with targeted contrast-enhanced ultrasound molecular imaging. Arterial elastic modulus and pulse wave transit time were assessed using ultrahigh frequency ultrasound and invasive hemodynamic measurements. Plaque size and composition were assessed by histology. Molecular imaging in nontreated mice detected a 2-fold increase in P-selectin expression, VCAM-1 expression, and platelet adhesion between 30 and 40 weeks of age. Apocynin reduced all of these endothelial events in a dose-dependent fashion (25% and 50% reduction in signal at 40 weeks for low- and high-dose apocynin). Apocynin also decreased aortic elastic modulus and increased the pulse transit time. On histology, apocynin reduced total monocyte accumulation in a dose-dependent manner as well as platelet adhesion, although total plaque area was reduced in only the high-dose apocynin treatment group. Conclusions-Inhibition of NADPH oxidase in advanced atherosclerosis reduces endothelial activation and platelet adhesion, which are likely responsible for the arrest of plaque growth and improvement of vascular mechanical properties.

Original languageEnglish (US)
Pages (from-to)74-82
Number of pages9
JournalCirculation: Cardiovascular Imaging
Volume6
Issue number1
DOIs
StatePublished - Jan 2013

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Molecular Imaging
NADPH Oxidase
Atherosclerosis
Blood Platelets
Antioxidants
Inflammation
Pulse Wave Analysis
P-Selectin
Vascular Cell Adhesion Molecule-1
Elastic Modulus
Platelet Activation
Therapeutics
Histology
Platelet Membrane Glycoproteins
LDL Receptors
acetovanillone
Thoracic Aorta
Blood Vessels
Monocytes
Reactive Oxygen Species

Keywords

  • Contrast ultrasound
  • Microbubbles
  • Oxidative stress
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis : Effects of antioxidant therapy with NADPH oxidase inhibition. / Liu, Yani; Davidson, Brian P.; Yue, Qi; Belcik, Todd; Xie, Aris; Inaba, Yoichi; McCarty, Owen; Tormoen, Garth W.; Zhao, Yan; Ruggeri, Zaverio M.; Kaufmann, Beat A.; Lindner, Jonathan.

In: Circulation: Cardiovascular Imaging, Vol. 6, No. 1, 01.2013, p. 74-82.

Research output: Contribution to journalArticle

Liu, Yani ; Davidson, Brian P. ; Yue, Qi ; Belcik, Todd ; Xie, Aris ; Inaba, Yoichi ; McCarty, Owen ; Tormoen, Garth W. ; Zhao, Yan ; Ruggeri, Zaverio M. ; Kaufmann, Beat A. ; Lindner, Jonathan. / Molecular imaging of inflammation and platelet adhesion in advanced atherosclerosis : Effects of antioxidant therapy with NADPH oxidase inhibition. In: Circulation: Cardiovascular Imaging. 2013 ; Vol. 6, No. 1. pp. 74-82.
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abstract = "Background-In atherosclerosis, local generation of reactive oxygen species amplifies the inflammatory response and contributes to plaque vulnerability. We used molecular imaging to test whether inhibition of NADPH oxidase with apocynin would reduce endothelial inflammatory activation and endothelial-platelet interactions, thereby interrupting progression to high-risk plaque phenotype. Methods and Results-Mice deficient for both the low-density lipoprotein receptor and Apobec-1 were studied at 30 weeks of age and again after 10 weeks with or without apocynin treatment (10 or 50 mg/kg per day orally). In vivo molecular imaging of vascular cell adhesion molecule-1 (VCAM 1) P-selectin, and platelet glycoprotein-1b (GPIb) in the thoracic aorta was performed with targeted contrast-enhanced ultrasound molecular imaging. Arterial elastic modulus and pulse wave transit time were assessed using ultrahigh frequency ultrasound and invasive hemodynamic measurements. Plaque size and composition were assessed by histology. Molecular imaging in nontreated mice detected a 2-fold increase in P-selectin expression, VCAM-1 expression, and platelet adhesion between 30 and 40 weeks of age. Apocynin reduced all of these endothelial events in a dose-dependent fashion (25{\%} and 50{\%} reduction in signal at 40 weeks for low- and high-dose apocynin). Apocynin also decreased aortic elastic modulus and increased the pulse transit time. On histology, apocynin reduced total monocyte accumulation in a dose-dependent manner as well as platelet adhesion, although total plaque area was reduced in only the high-dose apocynin treatment group. Conclusions-Inhibition of NADPH oxidase in advanced atherosclerosis reduces endothelial activation and platelet adhesion, which are likely responsible for the arrest of plaque growth and improvement of vascular mechanical properties.",
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T2 - Effects of antioxidant therapy with NADPH oxidase inhibition

AU - Liu, Yani

AU - Davidson, Brian P.

AU - Yue, Qi

AU - Belcik, Todd

AU - Xie, Aris

AU - Inaba, Yoichi

AU - McCarty, Owen

AU - Tormoen, Garth W.

AU - Zhao, Yan

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AB - Background-In atherosclerosis, local generation of reactive oxygen species amplifies the inflammatory response and contributes to plaque vulnerability. We used molecular imaging to test whether inhibition of NADPH oxidase with apocynin would reduce endothelial inflammatory activation and endothelial-platelet interactions, thereby interrupting progression to high-risk plaque phenotype. Methods and Results-Mice deficient for both the low-density lipoprotein receptor and Apobec-1 were studied at 30 weeks of age and again after 10 weeks with or without apocynin treatment (10 or 50 mg/kg per day orally). In vivo molecular imaging of vascular cell adhesion molecule-1 (VCAM 1) P-selectin, and platelet glycoprotein-1b (GPIb) in the thoracic aorta was performed with targeted contrast-enhanced ultrasound molecular imaging. Arterial elastic modulus and pulse wave transit time were assessed using ultrahigh frequency ultrasound and invasive hemodynamic measurements. Plaque size and composition were assessed by histology. Molecular imaging in nontreated mice detected a 2-fold increase in P-selectin expression, VCAM-1 expression, and platelet adhesion between 30 and 40 weeks of age. Apocynin reduced all of these endothelial events in a dose-dependent fashion (25% and 50% reduction in signal at 40 weeks for low- and high-dose apocynin). Apocynin also decreased aortic elastic modulus and increased the pulse transit time. On histology, apocynin reduced total monocyte accumulation in a dose-dependent manner as well as platelet adhesion, although total plaque area was reduced in only the high-dose apocynin treatment group. Conclusions-Inhibition of NADPH oxidase in advanced atherosclerosis reduces endothelial activation and platelet adhesion, which are likely responsible for the arrest of plaque growth and improvement of vascular mechanical properties.

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KW - Oxidative stress

KW - Platelets

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