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Author:
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Suarez-Giron, Monique C.; Castro-Grattoni, Anabel L.; Torres, Marta; Farré, Ramon; Barbé Illa, Ferran; Sánchez de la Torre, Manuel; Gozal, David; Picado, Cesar; Montserrat i Capdevila, Josep; Almendros, Isaac
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Notes:
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Study objectives: Chronic intermittent hypoxia (CIH), a hallmark feature of obstructive
sleep apnea (OSA), induces accelerated atherogenesis as well as aorta vascular
remodeling. Although the cyclooxygenase (COX) pathway has been proposed to
contribute to the cardiovascular consequences of OSA, the potential benefits of a
widely employed COX-inhibitor such (acetylsalicylic acid, ASA) on CIH-induced vascular
pathology are unknown. Therefore, we hypothesized that a common non-selective COX
inhibitor such as ASA would attenuate the aortic remodeling induced by CIH in mice.
Methods: 40 wild-type C57/BL6malemice were randomly allocated to CIH or normoxic
exposures (N) and treated with daily doses of ASA or placebo for 6 weeks. At the end
of the experiments, intima-media thickness (IMT), elastin disorganization (ED), elastin
fragmentation (EF), length between fragmented fiber endpoints (LFF), aortic wall collagen
abundance (AC) and mucoid deposition (MD) were assessed.
Results: Compared to N, CIH promoted significant increases in IMT (52.58 ± 2.82μm
vs. 46.07 ± 4.18μm, p < 0.003), ED (25.29 ± 14.60% vs. 4.74 ± 5.37%, p < 0.001),
EF (5.80 ± 2.04 vs. 3.06 ± 0.58, p < 0.001), LFF (0.65 ± 0.34% vs. 0.14 ± 0.09%,
p < 0.001), AC (3.43 ± 1.52% vs. 1.67 ± 0.67%, p < 0.001) and MD (3.40 ± 2.73 μm2
vs. 1.09 ± 0.72 μm2, p < 0.006). ASA treatment mitigated the CIH-induced alterations
in IMT: 44.07 ± 2.73μm; ED: 10.57 ± 12.89%; EF: 4.63 ± 0.88; LFF: 0.25 ± 0.17%
and AC: 0.90 ± 0.13% (p<0.05 for all comparisons).
Conclusions: ASA prevents the CIH-induced aortic vascular remodeling, and should
therefore be prospectively evaluated as adjuvant treatment in patients with OSA.
This work was supported by the Spanish Respiratory Society (SEPAR), SOCAP, the Associació Lleidatana de Respiratori (ALLER), and the Spanish Fondo de Investigaciones Sanitarias (PI14/00486 and PI14-00004), Instituto de Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”. DG is supported by National Institutes of Health grant HL130984. |
