Acetylsalicylic Acid Prevents Intermittent Hypoxia-Induced Vascular Remodeling in a Murine Model of Sleep Apnea

Abstract

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/BL6 male mice 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 ± 2.82 µm vs. 46.07 ± 4.18 µm, 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 µm 2 vs. 1.09 ± 0.72 µm 2 , p < 0.006). ASA treatment mitigated the CIH-induced alterations in IMT: 44.07 ± 2.73 µm; 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.

Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia

“…The fact that we used a conductive vessel such as the aorta, rather than a resistive vessel to assess vascular reactivity, might be kept in mind when trying to interpret the present findings to understand the development of systemic hypertension. However, recent studies showed that exposure of male mice to CIH induces consistent remodelling and proliferation of macrophages in the aorta, in line with the elevated cardiovascular risk in sleep apnoea patients.…”

Intermittent Hypoxia Alleviates β-Aminopropionitrile Monofumarate Induced Thoracic Aortic Dissection in C57BL/6 Mice

“…However, numerous studies have demonstrated that IH alone impaired vascular function and promoted vascular remodelling in normal mice. 35 Thus, it is speculated that the effects of IH on vascular ECM stability are dependent on BAPN administration. Second, the role of HIF-1a in IH of this mouse model was not detected.…”

The Role of Cyclooxygenase Enzymes and Microparticles in Obstructive Sleep Apnea Related Cerebrovascular Incidents

“…In healthy populations, exposure to IH might impair peripheral and cerebral vascular regulation, manifesting as increased resting blood pressure and slightly reduce cerebrovascular resistance during hypoxia. [2] The mechanisms involved in the occurrence of vascular dysfunction associated with OSA are multifactorial. IH-induced inflammation is a fundamental factor leading to increased cardiovascular and cerebrovascular morbidity.…”