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Title: Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})

Abstract

Exposure to ambient air particulate matter (particles less than 10 μm or PM{sub 10}) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM{sub 10}. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM{sub 10}/saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM{sub 10} exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM{sub 10} impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM{sub 10} increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatinmore » decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM{sub 10}. Taken together, statins protect against PM{sub 10}-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM{sub 10}) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal macrophages, lipid accumulation, and intimal area. • Lovastatin promoted smooth muscle cell recruitment into plaques. • Lovastatin reduced the expression of vasoactive mediators (iNOS, COX-2, and ET-1). • Lovastatin did not reduce blood lipid levels in PM{sub 10}-exposed rabbits.« less

Authors:
; ;  [1];  [1];  [2]; ;  [1]
  1. UBC James Hogg Research Centre, St. Paul's Hospital, University of British Columbia, Vancouver (Canada)
  2. Environmental Health Sciences and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa (Canada)
Publication Date:
OSTI Identifier:
22285389
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 272; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETYLCHOLINE; AORTA; ARTERIOSCLEROSIS; BALLOONS; BLOOD; COENZYMES; INDIUM OXIDES; INFLAMMATION; LIPIDS; MACROPHAGES; NITRIC OXIDE; PLAQUE FORMATION; RABBITS

Citation Formats

Miyata, Ryohei, Hiraiwa, Kunihiko, Cheng, Jui Chih, Bai, Ni, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Vincent, Renaud, Francis, Gordon A., Sin, Don D., and Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10}). United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.05.033.
Miyata, Ryohei, Hiraiwa, Kunihiko, Cheng, Jui Chih, Bai, Ni, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Vincent, Renaud, Francis, Gordon A., Sin, Don D., & Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca. Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10}). United States. https://doi.org/10.1016/J.TAAP.2013.05.033
Miyata, Ryohei, Hiraiwa, Kunihiko, Cheng, Jui Chih, Bai, Ni, Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Vincent, Renaud, Francis, Gordon A., Sin, Don D., and Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca. 2013. "Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})". United States. https://doi.org/10.1016/J.TAAP.2013.05.033.
@article{osti_22285389,
title = {Statins attenuate the development of atherosclerosis and endothelial dysfunction induced by exposure to urban particulate matter (PM{sub 10})},
author = {Miyata, Ryohei and Hiraiwa, Kunihiko and Cheng, Jui Chih and Bai, Ni and Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver and Vincent, Renaud and Francis, Gordon A. and Sin, Don D. and Van Eeden, Stephan F., E-mail: Stephan.vanEeden@hli.ubc.ca},
abstractNote = {Exposure to ambient air particulate matter (particles less than 10 μm or PM{sub 10}) has been shown to be an independent risk factor for the development and progression of atherosclerosis. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have well-established anti-inflammatory properties. The aim of this study was to determine the impact of statins on the adverse functional and morphological changes in blood vessels induced by PM{sub 10}. New Zealand White rabbits fed with a high fat diet were subjected to balloon injury to their abdominal aorta followed by PM{sub 10}/saline exposure for 4 weeks ± lovastatin (5 mg/kg/day) treatment. PM{sub 10} exposure accelerated balloon catheter induced plaque formation and increased intimal macrophages and lipid accumulation while lovastatin attenuated these changes and promoted smooth muscle cell recruitment into plaques. PM{sub 10} impaired vascular acetylcholine (Ach) responses and increased vasoconstriction induced by phenylephrine as assessed by wire myograph. Supplementation of nitric oxide improved the impaired Ach responses. PM{sub 10} increased the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in blood vessels and increased the plasma levels of endothelin-1 (ET-1). Incubation with specific inhibitors for iNOS, COX-2 or ET-1 in the myograph chambers significantly improved the impaired vascular function. Lovastatin decreased the expression of these mediators in atherosclerotic lesions and improved endothelial dysfunction. However, lovastatin was unable to reduce blood lipid levels to the baseline level in rabbits exposed to PM{sub 10}. Taken together, statins protect against PM{sub 10}-induced cardiovascular disease by reducing atherosclerosis and improving endothelial function via their anti-inflammatory properties. - Highlights: • Coarse particulate matter (PM{sub 10}) accelerated balloon injury-induced plaque formation. • Lovastatin decreased intimal macrophages, lipid accumulation, and intimal area. • Lovastatin promoted smooth muscle cell recruitment into plaques. • Lovastatin reduced the expression of vasoactive mediators (iNOS, COX-2, and ET-1). • Lovastatin did not reduce blood lipid levels in PM{sub 10}-exposed rabbits.},
doi = {10.1016/J.TAAP.2013.05.033},
url = {https://www.osti.gov/biblio/22285389}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 272,
place = {United States},
year = {Tue Oct 01 00:00:00 EDT 2013},
month = {Tue Oct 01 00:00:00 EDT 2013}
}