title: Intermittent Hypoxia Impairs Endothelial Function in Early Preatherosclerosis.
abstract: Intermittent hypoxia seems to be a major pathomechanism of obstructive sleep apnea-associated progression of atherosclerosis. The goal of the present study was to assess the influence of hypoxia on endothelial function depending on the initial stage of vasculopathy. We used 16 ApoE-/- mice were exposed to a 6-week-intermittent hypoxia either immediately (early preatherosclerosis) or after 5 weeks of high-cholesterol diet (advanced preatherosclerosis). Another 16 ApoE-/- mice under normoxia served as corresponding controls. Endothelial function was measured by an organ bath technique. Blood plasma CD31+/annexin V+ endothelial microparticles as well as sca1/flk1+ endothelial progenitor cells in blood and bone marrow were analyzed by flow cytometry. The findings were that intermittent hypoxia impaired endothelial function (56.6±6.2% of maximal phenylephrine-induced vasoconstriction vs. 35.2±4.1% in control) and integrity (increased percentage of endothelial microparticles: 0.28±0.05% vs. 0.15±0.02% in control) in early preatherosclerosis. Peripheral repair capacity expressed as the number of endothelial progenitor cells in blood was attenuated under hypoxia (2.0±0.5% vs. 5.3±1.9% in control), despite the elevated number of these cells in the bone marrow (2.0±0.4% vs. 1.1±0.2% in control). In contrast, endothelial function, as well as microparticle and endothelial progenitor cell levels were similar under hypoxia vs. control in advanced preatherosclerosis. We conclude that hypoxia aggravates endothelial dysfunction and destruction in early preatherosclerosis.
authors.affiliation: Department of Internal Medicine II - Cardiology, Pulmonology, University of Bonn, Sigmund-Freud-Str. 25, D-53105, Bonn, Germany, izabela.tuleta@ukb.uni-bonn.de.
authors.forename: I
authors.initials: I
authors.lastname: Tuleta
authors.forename: C N
authors.initials: CN
authors.lastname: França
authors.forename: D
authors.initials: D
authors.lastname: Wenzel
authors.forename: B
authors.initials: B
authors.lastname: Fleischmann
authors.forename: G
authors.initials: G
authors.lastname: Nickenig
authors.forename: N
authors.initials: N
authors.lastname: Werner
authors.forename: D
authors.initials: D
authors.lastname: Skowasch
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D000950:Antigens, Ly / Q000235:genetics / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000378:metabolism; D002784:Cholesterol / Q000008:administration & dosage; D059305:Diet, High-Fat; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D000860:Hypoxia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D010656:Phenylephrine / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D017304:Annexin A5; D000950:Antigens, Ly; D001057:Apolipoproteins E; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010656:Phenylephrine; D002784:Cholesterol; D040301:Vascular Endothelial Growth Factor Receptor-2