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

被引:66
作者
Castro-Grattoni, Anabel L. [1 ]
Alvarez-Buve, Roger [1 ]
Torres, Marta [2 ,4 ]
Farre, Ramon [3 ,4 ]
Montserrat, Josep M. [2 ,3 ,4 ]
Dalmases, Mireia [1 ,4 ]
Almendros, Isaac [3 ,4 ]
Barbe, Ferran [1 ,4 ]
Sanchez-de-la-Torre, Manuel [1 ,4 ]
机构
[1] Univ Lleida, Hosp Univ Arnau de Vilanova & Santa Maria, IRB Lleida, Resp Dept, Lleida, Catalonia, Spain
[2] Hosp Clin Barcelona, Dept Pneumol, Sleep Lab, Barcelona, Spain
[3] Univ Barcelona, Fac Med, Unitat Biofis & Bioengn, Barcelona 7, Spain
[4] Ctr Invest Biomed Red Enfermedades Resp CIBERES, Madrid, Spain
关键词
atherosclerosis recovery; cardiovascular disease; continuous positive airway pressure; intermittent hypoxia; obstructive sleep apnea; POSITIVE AIRWAY PRESSURE; SPONTANEOUSLY HYPERTENSIVE-RATS; LEFT-VENTRICULAR HYPERTROPHY; RANDOMIZED CONTROLLED-TRIAL; INTIMA-MEDIA THICKNESS; HEART-FAILURE; ANIMAL-MODELS; GENOMIC CONSEQUENCES; BLOOD-PRESSURE; MICE;
D O I
10.1016/j.chest.2015.11.010
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:1400 / 1408
页数:9
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