期刊
FRONTIERS IN PHYSIOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2021.663950
关键词
obstructive sleep apnea; atherosclerosis; intermittent hypoxia and hypercapnia; microbiome; metabolome
类别
资金
- NIH [T32 OD017863, K08 DK102902, R03 DK114536, R21 MH117780, R01 HL148801, P30 DK120515, P30 DK063491, P30 CA014195, UL1 TR001442]
- American Heart Association [16BGIA27760160]
The study reveals that intermittent hypercapnia (IC) can promote the formation of atherosclerosis, with different effects in different vascular beds, and the interaction between changes in gut microbiome and metabolome varies in distinct vascular beds.
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-beta-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据