title: Chronic intermittent hypoxia exposure-induced atherosclerosis: a brief review.
abstract: Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary, Critical Care and Sleep Medicine, The Feinstein Institute for Medical Research, Hofstra North Shore-LIJ School of Medicine, 350 Community Drive, Manhasset, NY, 11030, USA.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Song
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary, Critical Care and Sleep Medicine, The Feinstein Institute for Medical Research, Hofstra North Shore-LIJ School of Medicine, 350 Community Drive, Manhasset, NY, 11030, USA.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Fang
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary, Critical Care and Sleep Medicine, The Feinstein Institute for Medical Research, Hofstra North Shore-LIJ School of Medicine, 350 Community Drive, Manhasset, NY, 11030, USA.
authors.forename: Harly
authors.initials: H
authors.lastname: Greenberg
authors.affiliation: Centers for Heart and Lung Research, and Pulmonary, Critical Care and Sleep Medicine, The Feinstein Institute for Medical Research, Hofstra North Shore-LIJ School of Medicine, 350 Community Drive, Manhasset, NY, 11030, USA. Sliu@nshs.edu.
authors.forename: Shu Fang
authors.initials: SF
authors.lastname: Liu
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D002791:Cholesterol, Dietary / Q000009:adverse effects; D003094:Collagen / Q000378:metabolism; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D005487:Foam Cells / Q000276:immunology*; D055786:Gene Knockout Techniques; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000235:genetics / Q000276:immunology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D015398:Signal Transduction / Q000276:immunology; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000235:genetics / Q000276:immunology*
chemical_list: D002791:Cholesterol, Dietary; D016328:NF-kappa B; D003094:Collagen; D004549:Elastin
keywords: Atherosclerosis; Chronic intermittent hypoxia; Dyslipidemia; Inflammation; Obstructive sleep apnea