Abstract
Obstructive sleep apnea (OSA), a common sleep disorder characterized by intermittent hypoxia and hypercapnia (IHC), increases atherosclerosis risk. However, the contribution of intermittent hypoxia (IH) or intermittent hypercapnia (IC) in promoting atherosclerosis remains unclear. Since gut microbiota and metabolites have been implicated in atherosclerosis, we examined whether IH or IC alters the microbiome and metabolome to induce a pro-atherosclerotic state. Apolipoprotein E deficient mice (ApoE−/−), treated with IH or IC on a high-fat diet (HFD) for 10 weeks, were compared to Air controls. Atherosclerotic lesions were examined, gut microbiome was profiled using 16S rRNA gene amplicon sequencing and metabolome was assessed by untargeted mass spectrometry. In the aorta, IC-induced atherosclerosis was significantly greater than IH and Air controls (aorta, IC 11.1 ± 0.7% vs. IH 7.6 ± 0.4%, p < 0.05 vs. Air 8.1 ± 0.8%, p < 0.05). In the pulmonary artery (PA), however, IH, IC, and Air were significantly different from each other in atherosclerotic formation with the largest lesion observed under IH (PA, IH 40.9 ± 2.0% vs. IC 20.1 ± 2.6% vs. Air 12.2 ± 1.5%, p < 0.05). The most differentially abundant microbial families (p < 0.001) were Peptostreptococcaceae, Ruminococcaceae, and Erysipelotrichaceae. The most differentially abundant metabolites (p < 0.001) were tauro-β-muricholic acid, ursodeoxycholic acid, and lysophosphoethanolamine (18:0). We conclude that IH and IC (a) modulate atherosclerosis progression differently in distinct vascular beds with IC, unlike IH, facilitating atherosclerosis in both aorta and PA and (b) promote an atherosclerotic luminal gut environment that is more evident in IH than IC. We speculate that the resulting changes in the gut metabolome and microbiome interact differently with distinct vascular beds.
Highlights
Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive episodes of complete or partial upper airway obstruction during sleep
To find out the effect of these gas changes on atherosclerosis, 4h ttps://gnps.ucsd.edu/ProteoSAFe/static/gnps-splash.jsp 5h ttps://github.com/knightlab-analyses/longitudinal-osa we examined the atherosclerotic lesions in the aorta, aortic arch, and pulmonary artery (PA) after 10 weeks of intermittent hypoxia (IH) or intermittent hypercapnia (IC) exposure in the presence of high-fat diet (HFD)
OSA patients suffer from both episodic hypoxia and hypercapnia, only the impact of IH has been extensively studied from a cardiovascular viewpoint
Summary
Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive episodes of complete or partial upper airway obstruction during sleep. These apneic episodes lead to intermittent hypoxia and hypercapnia (IHC), wide intrathoracic pressure swings, as well as sleep fragmentation. OSA is independently associated with the elevated risk of myocardial infarction, stroke, and cardiovascular mortality, mainly through the promotion of severe atherosclerosis (Drager et al, 2011; Lui and Sau-Man, 2012; Sarkar et al, 2018; Tietjens et al, 2019). The pathophysiological mechanisms underlying OSA associated atherosclerotic risk are not completely understood
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.