Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea.

Background: 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 reversi...

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Detalles Bibliográficos
Autores: Castro Grattoni, Anabel Lourdes, Álvarez Buvé, Roger, Torres López, Marta, Farré Ventura, Ramón, Montserrat Canal, Josep María, Dalmases Clèries, Mireia, Almendros López, Isaac, Sánchez de la Torre, Manuel
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Universidad de Castilla-La Mancha
Repositorio:RUIdeRA. Repositorio Institucional de la UCLM
OAI Identifier:oai:ruidera.uclm.es:10578/41118
Acceso en línea:http://europepmc.org/abstract/med/26836908
https://hdl.handle.net/10578/41118
Access Level:acceso abierto
Palabra clave:Atherosclerosis recovery
Cardiovascular disease
Continuous positive airway pressure
Intermittent hypoxia
Obstructive sleep apnea
Descripción
Sumario:Background: 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.Methods: 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.Results: 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.Conclusions: 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.Keywords: atherosclerosis recovery; cardiovascular disease; continuous positive airway pressure; intermittent hypoxia; obstructive sleep apnea.