Atorvastatin attenuates intermittent hypoxia-induced myocardial oxidative stress in a mouse obstructive sleep apnea model

Abstract

Chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnea (OSA), is associated with various cardiovascular diseases. In the present study, we assessed the effect of the lipid reducing agent atorvastatin on CIH-induced myocardial oxidative stress and apoptosis in a mouse OSA model. Forty-eight C57BL/6J mice were evenly divided among normoxia + vehicle, normoxia + atorvastatin, CIH + vehicle, and CIH + atorvastatin groups. CIH consisted of a hypoxia-reoxygenation cycle in which oxygen concentrations fluctuated from 21% to 6% and back over two minutes for 8 hours each day (30 events/hour). CIH exposure continued for 12 weeks. Atorvastatin (5 mg/kg) was administered from week 6 through the end of the experiment. CIH increased malondialdehyde levels and decreased superoxide dismutase activity, total antioxidant capacity, and nuclear factor erythroid 2-related factor 2 levels in cardiac tissue, indicating a reduction in antioxidant activity. Atorvastatin significantly reversed those effects ( p < 0.05). CIH also increased B-cell lymphoma 2-associated protein X and cleaved caspased-3 levels as well as the myocardial apoptotic rate, as indicated by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Atorvastatin had no effect on those changes ( p > 0.05). Thus, atorvastatin administration exerts antioxidant but not anti-apoptotic effects after CIH and may therefore have therapeutic potential in OSA patients with cardiovascular comorbidities.

Obstructive Sleep Apnea-Associated Intermittent Hypoxia-Induced Immune Responses in Males, Pregnancies, and Offspring

“…Statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, are a class of cholesterol-lowering medications that also possess cardiovascular protective effects [93]. Atorvastatin, which shows efficacy in attenuating chronic IH-induced myocardial and neural inflammation via suppressing TLR4/MyD88/NF-κB signaling pathways [33,40,94], also suppresses NLRP3 inflammasome activation [95], although this has not been tested in IH models. A recent clinical trial indicates promising protective effects of atorvastatin against cardiovascular risks in OSA patients [96].…”

Simvastatin-Loaded Nanoniosome Protects H9c2 Cells from Oxygen-Glucose Deprivation/Reperfusion Injury by Downregulating Inflammation

“…However, the oral administration of this lipophilic statin has disadvantages such as low bioavailability (less than 5%) and a short half-life (1-2 h) due to the degradation within the gastrointestinal tract and hepatic first-pass metabolism that limits its efficacy and potency [ 9 ] . Although there is ample evidence that lipophilic statins, such as SIM, are more efficient than hydrophilic statins in improving cardiac function and decreasing inflammation, minimizing their drawbacks is still needed [ 10 , 11 ] .…”