title: Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea.
abstract: Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment.
  
  
  
  We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia.
  
  
  
  Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment.
  
  
  
  The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases.
authors.affiliation: Respiratory Department, Hospital Universiti Arnau de Vilanova and Santa Maria, IRB Lleida, University of Lleida, Lleida, Catalonia, Spain.
authors.forename: Anabel L
authors.initials: AL
authors.lastname: Castro-Grattoni
authors.affiliation: Respiratory Department, Hospital Universiti Arnau de Vilanova and Santa Maria, IRB Lleida, University of Lleida, Lleida, Catalonia, Spain.
authors.forename: Roger
authors.initials: R
authors.lastname: Alvarez-Buvé
authors.affiliation: Sleep Laboratory, Pneumology Department, Hospital Clinic of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Torres
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, and the Institut Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
authors.affiliation: Sleep Laboratory, Pneumology Department, Hospital Clinic of Barcelona, Barcelona, Spain; Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, and the Institut Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Montserrat
authors.affiliation: Respiratory Department, Hospital Universiti Arnau de Vilanova and Santa Maria, IRB Lleida, University of Lleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Dalmases
authors.affiliation: Unitat de Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, and the Institut Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Almendros
authors.affiliation: Respiratory Department, Hospital Universiti Arnau de Vilanova and Santa Maria, IRB Lleida, University of Lleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Barbé
authors.affiliation: Respiratory Department, Hospital Universiti Arnau de Vilanova and Santa Maria, IRB Lleida, University of Lleida, Lleida, Catalonia, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain. Electronic address: sanchezdelatorre@gmail.com.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-de-la-Torre
mesh_terms: D000818:Animals; D001011:Aorta / Q000000981:diagnostic imaging / Q000473:pathology; D002319:Cardiovascular System / Q000503:physiopathology; D004195:Disease Models, Animal; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000503:physiopathology; D013223:Statistics as Topic; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D066253:Vascular Remodeling / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology*
keywords: atherosclerosis recovery; cardiovascular disease; continuous positive airway pressure; intermittent hypoxia; obstructive sleep apnea