help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Published ahead of print on March 1, 2007, doi:10.1164/rccm.200612-1771OC
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online Supplement
Right arrow All Versions of this Article:
200612-1771OCv1
175/12/1290    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Related articles in AJRCCM
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Savransky, V.
Right arrow Articles by Polotsky, V. Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Savransky, V.
Right arrow Articles by Polotsky, V. Y.
American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 1290-1297, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200612-1771OC

Original Article

Chronic Intermittent Hypoxia Induces Atherosclerosis

Vladimir Savransky1, Ashika Nanayakkara1, Jianguo Li1, Shannon Bevans1, Philip L. Smith1, Annabelle Rodriguez2 and Vsevolod Y. Polotsky1

1 Division of Pulmonary and Critical Care Medicine and 2 Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University, Baltimore, Maryland

Correspondence and requests for reprints should be addressed to Vsevolod Y. Polotsky, M.D., Ph.D., Division of Pulmonary and Critical Care Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail: vpolots1{at}jhmi.edu

Rationale: Obstructive sleep apnea, a condition leading to chronic intermittent hypoxia (CIH), is associated with hyperlipidemia, atherosclerosis, and a high cardiovascular risk. A causal link between obstructive sleep apnea and atherosclerosis has not been established.

Objectives: The objective of the present study was to examine whether CIH may induce atherosclerosis in C57BL/6J mice.

Methods: Forty male C57BL/6J mice, 8 weeks of age, were fed either a high-cholesterol diet or a regular chow diet and subjected either to CIH or intermittent air (control conditions) for 12 weeks.

Measurements and Main Results: Nine of 10 mice simultaneously exposed to CIH and high-cholesterol diet developed atherosclerotic lesions in the aortic origin and descending aorta. In contrast, atherosclerosis was not observed in mice exposed to intermittent air and a high-cholesterol diet or in mice exposed to CIH and a regular diet. A high-cholesterol diet resulted in significant increases in serum total and low-density lipoprotein cholesterol levels and a decrease in high-density lipoprotein cholesterol. Compared with mice exposed to intermittent air and a high-cholesterol diet, combined exposure to CIH and a high-cholesterol diet resulted in marked progression of dyslipidemia with further increases in serum total cholesterol and low-density lipoprotein cholesterol (124 ± 4 vs. 106 ± 6 mg/dl; p < 0.05), a twofold increase in serum lipid peroxidation, and up-regulation of an important hepatic enzyme of lipoprotein secretion, stearoyl-coenzyme A desaturase-1.

Conclusions: CIH causes atherosclerosis in the presence of diet-induced dyslipidemia.

Key Words: obstructive sleep apnea • lipids • hypoxia • mouse • stearoyl-coenzyme A desaturase


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Obstructive sleep apnea is associated with atherosclerosis, and the severity of atherosclerosis correlates with the severity of hypoxia. The causal relationships between sleep apnea and atherosclerosis are unknown.

What This Study Adds to the Field
Chronic intermittent hypoxia, similar to that observed in patients with sleep apnea, causes atherosclerotic lesions in the aorta of male C57BL/6J mice, which are resistant to the disease in the absence of hypoxia.

 

Related articles in AJRCCM:

Obstructive Sleep Apnea and Atherosclerosis: A New Paradigm
Geraldo Lorenzi-Filho and Luciano F. Drager
AJRCCM 2007 175: 1219-1221. [Full Text]  



This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
R. L. Horner and T. D. Bradley
Update in Sleep and Control of Ventilation 2007
Am. J. Respir. Crit. Care Med., May 1, 2008; 177(9): 947 - 951.
[Full Text] [PDF]

Home page
 ChestHome page
D. Sorajja, A. S. Gami, V. K. Somers, T. R. Behrenbeck, A. Garcia-Touchard, and F. Lopez-Jimenez
Independent Association Between Obstructive Sleep Apnea and Subclinical Coronary Artery Disease
Chest, April 1, 2008; 133(4): 927 - 933.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
O. S. Capdevila, L. Kheirandish-Gozal, E. Dayyat, and D. Gozal
Pediatric Obstructive Sleep Apnea: Complications, Management, and Long-term Outcomes
Proceedings of the ATS, February 15, 2008; 5(2): 274 - 282.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
T. Yokoe, L. C. Alonso, L. C. Romano, T. C. Rosa, Robert. M. O'Doherty, A. Garcia-Ocana, K. Minoguchi, and C. P. O'Donnell
Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic {beta}-cell replication in mice
J. Physiol., February 1, 2008; 586(3): 899 - 911.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Dematteis, C. Julien, C. Guillermet, N. Sturm, S. Lantuejoul, M. Mallaret, P. Levy, and E. Gozal
Intermittent Hypoxia Induces Early Functional Cardiovascular Remodeling in Mice
Am. J. Respir. Crit. Care Med., January 15, 2008; 177(2): 227 - 235.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
R. Amin, V. K. Somers, K. McConnell, P. Willging, C. Myer, M. Sherman, G. McPhail, A. Morgenthal, M. Fenchel, J. Bean, et al.
Activity-Adjusted 24-Hour Ambulatory Blood Pressure and Cardiac Remodeling in Children with Sleep Disordered Breathing
Hypertension, January 1, 2008; 51(1): 84 - 91.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. GenomicsHome page
J. Li, A. Nanayakkara, J. Jun, V. Savransky, and V. Y. Polotsky
Effect of deficiency in SREBP cleavage-activating protein on lipid metabolism during intermittent hypoxia
Physiol Genomics, October 19, 2007; 31(2): 273 - 280.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. Yumino and T. D. Bradley
Pathogenesis of Atherosclerosis: Is Obstructive Sleep Apnea the New Kid on the Block?
Am. J. Respir. Crit. Care Med., October 1, 2007; 176(7): 634 - 635.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
L. F. Drager, L. A. Bortolotto, A. C. Figueiredo, E. M. Krieger, and G. Lorenzi-Filho
Effects of Continuous Positive Airway Pressure on Early Signs of Atherosclerosis in Obstructive Sleep Apnea
Am. J. Respir. Crit. Care Med., October 1, 2007; 176(7): 706 - 712.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
V. Savransky, S. Bevans, A. Nanayakkara, J. Li, P. L. Smith, M. S. Torbenson, and V. Y. Polotsky
Chronic intermittent hypoxia causes hepatitis in a mouse model of diet-induced fatty liver
Am J Physiol Gastrointest Liver Physiol, October 1, 2007; 293(4): G871 - G877.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
M. Moss
Clinical Year in Review II: Interstitial Lung Disease, Sepsis, Pulmonary Infections, and Sleep Medicine
Proceedings of the ATS, September 15, 2007; 4(6): 482 - 488.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. Lorenzi-Filho and L. F. Drager
Obstructive Sleep Apnea and Atherosclerosis: A New Paradigm
Am. J. Respir. Crit. Care Med., June 15, 2007; 175(12): 1219 - 1221.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2007 American Thoracic Society