Chronic intermittent hypoxia induces atherosclerosis

Vladimir Savransky, Ashika Nanayakkara, Jianguo Li, Shannon Bevans, Philip L. Smith, Annabelle Rodriguez, Vsevolod Y. Polotsky

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1290-1297
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume175
Issue number12
DOIs
StatePublished - Jun 15 2007

Keywords

  • Hypoxia
  • Lipids
  • Mouse
  • Obstructive sleep apnea
  • Stearoylcoenzyme A desaturase

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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