scholarly journals Chronic Intermittent Hypoxia Participates in the Pathogenesis of Atherosclerosis and Perturbs the Formation of Intestinal Microbiota

2021 ◽  
Vol 11 ◽  
Author(s):  
Chaowei Hu ◽  
Pan Wang ◽  
Yunyun Yang ◽  
Juan Li ◽  
Xiaolu Jiao ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Intermittent Hypoxia ◽  
Causal Effect ◽  
Atherosclerotic Lesion ◽  
Chronic Intermittent Hypoxia ◽  
Physiological Status ◽  
Microbial Composition ◽  
Obstructive Sleep ◽  
Increased Risk ◽  
Rdna Sequencing

Chronic intermittent hypoxia (CIH) is the prominent signature of highly prevalent obstructive sleep apnea (OSA) pathophysiology, which leads to increased risk and aggravation of atherosclerotic cardiovascular diseases. However, whether intestinal microbiota is implicated in the mechanisms linking CIH to arteriosclerosis (AS) pathogenesis remains unclear. The association of CIH with the development of altered gut microbiota (GM) may provide the opportunity to develop preventive strategies for atherosclerotic cardiovascular risk reduction. Animal models of apolipoprotein E-deficient (apoE-/-) mice treated with high-fat diet (HFD) and subjected to CIH conditions was applied to mimic the AS observed in patients with OSA. The physiological status and atherosclerotic lesion formation were confirmed by histological analysis. 16S rDNA sequencing of fecal samples was conducted to determine the changes in gut microbial composition. Morphometric analysis demonstrated that CIH caused aggravated atherosclerotic lesions and facilitated AS in apoE-/- mice treated with HFD. The gut bacteria was significantly varied in AS and AS+CIH mice compared with that in the control mice. Significantly perturbed GM profiles were detected in AS mice with and without CIH, with altered microbial α- and β- diversity and shifts in bacterial compositions at phylum and genus levels. While the difference between AS and AS+CIH was observed at different bacteria taxa levels. Aggravation of reduced Sutterella and increased Halomonas, Halomonadaceae and Oceanospirillales was noted in CIH-treated AS mice. The correlation of intestinal bacterial parameters with pathological changes in artery indicated complicated interactions under CIH-induced GM dysbiosis. Furthermore, the gut microbial functions in the potential ability of replication recombination and repair proteins, glycan biosynthesis and metabolism, as well as metabolism of cofactors and vitamins were identified to be further suppressed by CIH. Our findings demonstrated a causal effect of CIH on GM alterations in AS mice and suggested that the disordered GM features in AS development were deteriorated by CIH, which may be associated with AS aggravation. Preventative strategies targeting gut microbiome are highly recommended for intervention of OSA-related AS.

scholarly journals Ratio of Klebsiella/Bifidobacterium in early life correlates with later development of paediatric allergy

2017 ◽  
Vol 8 (5) ◽  
pp. 681-695 ◽  
Author(s):  
J.S.Y. Low ◽  
S.-E. Soh ◽  
Y.K. Lee ◽  
K.Y.C. Kwek ◽  
J.D. Holbrook ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Allergic Disease ◽  
Early Life ◽  
16S Rrna Gene Sequencing ◽  
Early Infancy ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Healthy Infants ◽  
Increased Risk ◽  
Paediatric Allergy

Several studies have reported that intestinal microbial colonisation patterns differ between non-allergic and allergic infants. However, the microbial signature underlying the pathogenesis of allergies remains unclear. We aim to gain insight into the development of the intestinal microbiota of healthy infants and infants who develop allergy in early life, and identify potential microbiota biomarkers of later allergic disease. Using a case-control design in a Chinese sub-cohort of a Singaporean birth cohort (GUSTO), we utilised 16S rRNA gene sequencing to assess intestinal microbial composition and diversity of 21 allergic and 18 healthy infants at 3 weeks, 3 months and 6 months of age, and correlated the microbiota with allergy at ages 18 and 36 months. Pronounced differences in intestinal microbiota composition between allergic and healthy infants were observed at 3 months of age. The intestine of healthy infants was colonised with higher abundance of commensal Bifidobacterium. Conversely, Klebsiella, an opportunistic pathogen, was significantly enriched in the allergic infants. Interestingly, infants with a high Klebsiella/Bifidobacterium (K/B) ratio (above the population median K/B ratio) at age 3 months had an odds ratio of developing allergy by 3 years of age of 9.00 (95% confidence interval 1.46-55.50) compared to those with low K/B ratio. This study demonstrated a relationship between the ratio of genera Klebsiella and Bifidobacterium during early infancy and development of paediatric allergy in childhood. Our study postulates that an elevated K/B ratio in early infancy could be a potential indicator of an increased risk of allergy development. This line of research might enable future intervention strategies in early life to prevent or treat allergy. Our study provides new insights into microbial signatures associated with childhood allergy, in particular, suggests that an elevated K/B ratio could be a potential early-life microbiota biomarker of allergic disease.

scholarly journals Vascular and renal telomere shortening in mice exposed to chronic intermittent hypoxia

2021 ◽  
Author(s):  
Mohammad Badran ◽  
Bisher Abuyassin ◽  
Najib Ayas ◽  
Don D. Sin ◽  
Ismail Laher
Keyword(s):  
Obstructive Sleep Apnea ◽  
Chronic Condition ◽  
Intermittent Hypoxia ◽  
Kidney Diseases ◽  
Chronic Intermittent Hypoxia ◽  
Telomere Shortening ◽  
Chronic Kidney Diseases ◽  
Biomarkers Of Aging ◽  
Obstructive Sleep ◽  
Renal Aging

AbstractObstructive sleep apnea (OSA) is a chronic condition characterized by chronic intermittent hypoxia (IH) and is associated with cardiovascular (CVD) and chronic kidney diseases (CKD). There is increased biomarkers of aging, such as telomere shortening, in patients with OSA. We assessed telomere lengths in aortic and renal tissues from mice exposed to 8 weeks of IH using a PCR protocol, and demonstrate significant telomere shortening in both tissues. This data indicates that IH, a hallmark of OSA, can accelerate vascular and renal aging that may contribute to OSA-induced CVD and CKD

scholarly journals Tempol Alleviates Chronic Intermittent Hypoxia-Induced Pancreatic Injury Through Repressing Inflammation and Apoptosis

2019 ◽  
pp. 445-455
Author(s):  
Y. WANG ◽  
L. AI ◽  
B. HAI ◽  
Y. CAO ◽  
R. LI ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Pancreatic Injury ◽  
Protective Role ◽  
Pancreatic Tissue ◽  
Mitogen Activated Protein Kinase ◽  
Chronic Intermittent Hypoxia ◽  
Obstructive Sleep ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
Oxide Synthase

Obstructive sleep apnea (OSA) has been demonstrated to be implicated in disorder of insulin secretion and diabetes mellitus. In this study, we aimed to evaluate the protective role of tempol, a powerful antioxidant, in chronic intermittent hypoxia (IH)-induced pancreatic injury. The rat model of OSA was established by IH exposure. The pathological changes, increased blood-glucose level, and raised proinsulin/insulin ratio in pancreatic tissues of rats received IH were effectively relieved by tempol delivery. In addition, the enhanced levels of pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and inflammatory mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible nitric oxide synthase (iNOS) in pancreatic tissue were suppressed by tempol. Moreover, tempol inhibited IH-induced apoptosis in pancreatic tissue as evidenced by upregulated Bcl-2 level, and downregulated Bax and cleaved caspase-3 levels. Finally, the abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways induced by IH was restrained by tempol administration. In summary, our study demonstrates that tempol relieves IH-induced pancreatic injury by inhibiting inflammatory response and apoptosis, which provides theoretical basis for tempol as an effective treatment for OSA-induced pancreatic injury.

Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney

2021 ◽  
Vol 320 (1) ◽  
pp. F1-F16
Author(s):  
Sara AlMarabeh ◽  
Julie O’Neill ◽  
Jeremy Cavers ◽  
Eric F. Lucking ◽  
Ken D. O’Halloran ◽  
...  
Keyword(s):  
High Pressure ◽  
Volume Expansion ◽  
Intermittent Hypoxia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Low Pressure ◽  
Chronic Intermittent Hypoxia ◽  
Transient Receptor Potential Vanilloid ◽  
Baroreflex Control ◽  
Obstructive Sleep

We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na+ excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH 1) does not impair the low-pressure baroreflex control of RSNA; 2) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; 3) can elicit hypertension in the absence of kidney injury; and 4) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.

scholarly journals Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ying Zou ◽  
Wei Wang ◽  
Xinshi Nie ◽  
Jian Kang
Keyword(s):  
Obstructive Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Magnetic Stimulation ◽  
Upper Airway ◽  
Emg Activity ◽  
Chronic Intermittent Hypoxia ◽  
Experimental Conditions ◽  
Obstructive Sleep ◽  
Long Term Facilitation

Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8) and the CIH group (n=8). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.

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