Increased MCP-1 gene expression in monocytes of severe OSA patients and under intermittent hypoxia

2015 ◽  
Vol 20 (1) ◽  
pp. 425-433 ◽  
Author(s):  
Li-Pang Chuang ◽  
Ning-Hung Chen ◽  
Yuling Lin ◽  
Wen-Shan Ko ◽  
Jong-Hwei S. Pang
Keyword(s):  
Gene Expression ◽  
Intermittent Hypoxia

Abstract 356: IKK-Beta Deletion Alleviates the Atherogenetic Effect of Intermittent Hypoxia Induced Macrophage Foam Cell Formation

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Toshihiro Imamura ◽  
Iain S Hartley ◽  
Abdull J Massri ◽  
Orit Poulsen ◽  
Dan Zhou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Intermittent Hypoxia ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Wild Type ◽  
Nf Kappa B ◽  
Macrophage Foam Cell ◽  
Obstructive Sleep ◽  
Intracellular Cholesterol

Background: Obstructive sleep apnea syndrome (OSAS) is a common sleeping disorder characterized by intermittent hypoxia (IH). Clinical studies have previously shown an independent association between obstructive sleep apnea and atherosclerosis. Furthermore, it has been previously shown that such a predisposition to atherosclerosis in OSAS patient can be caused by various inflammatory mediators, particularly the NF-kappa B (NF-kB) pathway. Foam cells or lipid-laden macrophages in the atherosclerotic lesion have been well documented as a hallmark of atherosclerosis; however, the contribution of IH, such as in OSAS, to foam cell formation is not yet fully understood. Previous observations have led us to hypothesized that IH induces macrophage foam cell formation due to the activation of NF-kappa B pathway. Methods: Myeloid restricted IKK-beta deleted mice were generated by a Cre/lox recombination system to inactivate the NF-kB pathway in macrophages. Thioglycollate-elicited peritoneal macrophages were incubated with 200 μg/ml of low-density lipoprotein and simultaneously exposed to either IH (Normoxia: 8min, 0.5% O2: 10min) or normoxia for 24 hours. After exposure, the extent of foam cell formation was assessed by quantification of intracellular cholesterol. Finally, we compared the differences in gene expression using RNA-seq between wild type and IKK-beta deleted macrophages exposed to either IH or normoxia for 24 hours. Results: IH significantly increased total cholesterol in wild type macrophages (63.4±3.3 μg/mg of cellular protein, n=9) in comparison to normoxia (51.2±1.6). Interestingly, such increase in intracellular cholesterol in response to IH-exposure was abolished by IKK-beta deletion (IH 52.4±1.1; normoxia 50.0±1.6 n=8), suggesting that NF-kB pathway regulated gene expression is critical for IH-induced foam cell formation. Indeed, we have found that NF-kB knockout abolished IH-induced expressional alterations in 364 genes, which are potential candidates for regulating intracellular cholesterol. Conclusion: NF-kB activation plays a critical role in IH-induced macrophage foam cell formation.

Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters

2014 ◽  
Vol 307 (11) ◽  
pp. H1626-H1633 ◽  
Author(s):  
Ryuji Kato ◽  
Atsuo Nomura ◽  
Aiji Sakamoto ◽  
Yuki Yasuda ◽  
Koyuha Amatani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Sleep Apnea ◽  
Intermittent Hypoxia ◽  
Left Ventricular ◽  
Hydrogen Gas ◽  
Normal Male ◽  
Syrian Hamsters ◽  
Failing Heart ◽  
Mitral Annulus Velocity

The prevalence of sleep apnea is very high in patients with heart failure (HF). The aims of this study were to investigate the influence of intermittent hypoxia (IH) on the failing heart and to evaluate the antioxidant effect of hydrogen gas. Normal male Syrian hamsters ( n = 22) and cardiomyopathic (CM) hamsters ( n = 33) were exposed to IH (repeated cycles of 1.5 min of 5% oxygen and 5 min of 21% oxygen for 8 h during the daytime) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was inhaled by some CM hamsters during hypoxia. IH increased the ratio of early diastolic mitral inflow velocity to mitral annulus velocity (E/e′, 21.8 vs. 16.9) but did not affect the LV ejection fraction (EF) in normal Syrian hamsters. However, IH increased E/e′ (29.4 vs. 21.5) and significantly decreased the EF (37.2 vs. 47.2%) in CM hamsters. IH also increased the cardiomyocyte cross-sectional area (672 vs. 443 μm2) and interstitial fibrosis (29.9 vs. 9.6%), along with elevation of oxidative stress and superoxide production in the left ventricular (LV) myocardium. Furthermore, IH significantly increased the expression of brain natriuretic peptide, β-myosin heavy chain, c- fos, and c- jun mRNA in CM hamsters. Hydrogen gas inhalation significantly decreased both oxidative stress and embryonic gene expression, thus preserving cardiac function in CM hamsters. In conclusion, IH accelerated LV remodeling in CM hamsters, at least partly by increasing oxidative stress in the failing heart. These findings might explain the poor prognosis of patients with HF and sleep apnea.

scholarly journals miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling

2020 ◽  
Vol 21 (3) ◽  
pp. 999
Author(s):  
Yung-Che Chen ◽  
Po-Yuan Hsu ◽  
Mao-Chang Su ◽  
Chien-Hung Chin ◽  
Chia-Wei Liou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Cell Apoptosis ◽  
Intermittent Hypoxia ◽  
Target Genes ◽  
Apnea Hypopnea Index ◽  
Gene Expressions ◽  
Obstructive Sleep ◽  
Tnf Α

The purpose of this study is to explore the anti-inflammatory role of microRNAs (miR)-21 and miR-23 targeting the TLR/TNF-α pathway in response to chronic intermittent hypoxia with re-oxygenation (IHR) injury in patients with obstructive sleep apnea (OSA). Gene expression levels of the miR-21/23a, and their predicted target genes were assessed in peripheral blood mononuclear cells from 40 treatment-naive severe OSA patients, and 20 matched subjects with primary snoring (PS). Human monocytic THP-1 cell lines were induced to undergo apoptosis under IHR exposures, and transfected with miR-21-5p mimic. Both miR-21-5p and miR-23-3p gene expressions were decreased in OSA patients as compared with that in PS subjects, while TNF-α gene expression was increased. Both miR-21-5p and miR-23-3p gene expressions were negatively correlated with apnea hypopnea index and oxygen desaturation index, while TNF-α gene expression positively correlated with apnea hypopnea index. In vitro IHR treatment resulted in decreased miR-21-5p and miR-23-3p expressions. Apoptosis, cytotoxicity, and gene expressions of their predicted target genes—including TNF-α, ELF2, NFAT5, HIF-2α, IL6, IL6R, EDNRB, and TLR4—were all increased in response to IHR, while all were reversed with miR-21-5p mimic transfection under IHR condition. The findings provide biological insight into mechanisms by which IHR-suppressed miRs protect cell apoptosis via inhibit inflammation, and indicate that over-expression of the miR-21-5p may be a new therapy for OSA.

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