Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model

Cuiqing Liu, Rajagopal Desikan, Zhekang Ying, Liubov Gushchina, Thomas Kampfrath, Jeffrey Deiuliis, Aixia Wang, Xiaohua Xu, Jixin Zhong, Xiaoquan Rao, Qinghua Sun, Andrei Maiseyeu, Sampath Parthasarathy, Sanjay Rajagopalan

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Inflammation and oxidative stress play fundamental roles in the pathogenesis of atherosclerosis. Myeloperoxidase has been extensively implicated as a key mediator of inflammatory and redox-dependent processes in atherosclerosis. However, the effect of synthetic myeloperoxidase inhibitors on atherosclerosis has been insufficiently studied. In this study, ApoE-/- mice were randomized to low- and high-dose INV-315 groups for 16 weeks on high-fat diet. INV-315 resulted in reduced plaque burden and improved endothelial function in response to acetylcholine. These effects occurred without adverse events or changes in body weight or blood pressure. INV-315 treatment resulted in a decrease in iNOS gene expression, superoxide production and nitrotyrosine content in the aorta. Circulating IL-6 and inflammatory CD11b+/Ly6Glow/7/4hi monocytes were significantly decreased in response to INV-315 treatment. Acute pretreatment with INV-315 blocked TNFα-mediated leukocyte adhesion in cremasteric venules and inhibited myeloperoxidase activity. Cholesterol efflux was significantly increased by high-dose INV-315 via ex-vivo reverse cholesterol transport assays. Our results suggest that myeloperoxidase inhibition may exert anti-atherosclerotic effects via inhibition of oxidative stress and enhancement of cholesterol efflux. These findings demonstrate a role for pharmacologic modulation of myeloperoxidase in atherosclerosis.

Original languageEnglish (US)
Article numbere50767
JournalPloS one
Volume7
Issue number12
DOIs
StatePublished - Dec 10 2012
Externally publishedYes

Fingerprint

myeloperoxidase
atherosclerosis
Peroxidase
Atherosclerosis
mice
Oxidative stress
Cholesterol
cholesterol
Oxidative Stress
oxidative stress
dosage
Body Weight Changes
Venules
body weight changes
Blood pressure
High Fat Diet
Apolipoproteins E
acetylcholine
high fat diet
Nutrition

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Liu, C., Desikan, R., Ying, Z., Gushchina, L., Kampfrath, T., Deiuliis, J., ... Rajagopalan, S. (2012). Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model. PloS one, 7(12), [e50767]. https://doi.org/10.1371/journal.pone.0050767

Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model. / Liu, Cuiqing; Desikan, Rajagopal; Ying, Zhekang; Gushchina, Liubov; Kampfrath, Thomas; Deiuliis, Jeffrey; Wang, Aixia; Xu, Xiaohua; Zhong, Jixin; Rao, Xiaoquan; Sun, Qinghua; Maiseyeu, Andrei; Parthasarathy, Sampath; Rajagopalan, Sanjay.

In: PloS one, Vol. 7, No. 12, e50767, 10.12.2012.

Research output: Contribution to journalArticle

Liu, C, Desikan, R, Ying, Z, Gushchina, L, Kampfrath, T, Deiuliis, J, Wang, A, Xu, X, Zhong, J, Rao, X, Sun, Q, Maiseyeu, A, Parthasarathy, S & Rajagopalan, S 2012, 'Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model', PloS one, vol. 7, no. 12, e50767. https://doi.org/10.1371/journal.pone.0050767
Liu C, Desikan R, Ying Z, Gushchina L, Kampfrath T, Deiuliis J et al. Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model. PloS one. 2012 Dec 10;7(12). e50767. https://doi.org/10.1371/journal.pone.0050767
Liu, Cuiqing ; Desikan, Rajagopal ; Ying, Zhekang ; Gushchina, Liubov ; Kampfrath, Thomas ; Deiuliis, Jeffrey ; Wang, Aixia ; Xu, Xiaohua ; Zhong, Jixin ; Rao, Xiaoquan ; Sun, Qinghua ; Maiseyeu, Andrei ; Parthasarathy, Sampath ; Rajagopalan, Sanjay. / Effects of a Novel Pharmacologic Inhibitor of Myeloperoxidase in a Mouse Atherosclerosis Model. In: PloS one. 2012 ; Vol. 7, No. 12.
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