Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea

Emin, Memet; Wang, Gang; Castagna, F.; Rodriguez-Lopez, Josanna; Wahab, Romina; Wang, Jing; Adams, Tessa; Wei, Ying; Jelić, Sanja

doi:10.1126/scitranslmed.aad0634

Cited by 40 publications

(30 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…described that the internalisation of CD59, an inhibitor of C5b‐9, is augmented in OSA. This could contribute to a more prominent complement effect in the development of atherosclerosis (Emin et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…This and our study suggest that C3a may more strongly reflect complement activation than SC5b‐9. Of note, unchanged levels of SC5b‐9 may still lead to an enhanced MAC effect, as lower levels of CD59, a potent inhibitor of C5b‐9, were found in OSA (Emin et al., ).…”

Section: Discussionmentioning

confidence: 99%

“…Although complement factors have not been previously measured in OSA, their potential involvement is supported by two stud- described that the internalisation of CD59, an inhibitor of C5b-9, is augmented in OSA. This could contribute to a more prominent complement effect in the development of atherosclerosis (Emin et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Complement system activation in obstructive sleep apnea

Horváth

Tárnoki

et al. 2018

Journal of Sleep Research

View full text Add to dashboard Cite

The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b-9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 [0-338.5] ng ml ) and in the morning (85.5 [0-247.8] ng ml ) compared with controls (30.3 [0-176.8] ng ml and 36.3 [0-167.1] ng ml , evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b-9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 [1.6-47.4] ng ml to 9.3 [0-46.4] ng ml , p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C-reactive protein and low high-density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Complement system activation in obstructive sleep apnea

Horváth

Tárnoki

et al. 2018

Journal of Sleep Research

View full text Add to dashboard Cite

show abstract

“…Of note, the overall pathways identified in the bioinformatic analyses have been previously implicated either directly or indirectly in the pathophysiology of sleep apnea perturbations triggering vascular dysfunction. 61,62 The identification of mRNAs and miRNAs in exosomes and the ability of the transferred exosomal miRNA and mRNA to be translated in target cells constitute a major breakthrough in exosome biology. 52 In particular, exosomal miRNAs are playing an important role in cell-to-cell communication and involved in a multitude of functions, both physiological and pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Khalyfa

Zhang

Khalyfa

et al. 2016

Sleep

View full text Add to dashboard Cite

Study Objective: Intermittent hypoxia (IH) is associated with increased risk of cardiovascular disease. Exosomes are secreted by most cell types and released in biological fluids, including plasma, and play a role in modifying the functional phenotype of target cells. Using an experimental human model of IH, we investigated potential exosome-derived biomarkers of IH-induced vascular dysfunction. Methods: Ten male volunteers were exposed to room air (D0), IH (6 h/day) for 4 days (D4) and allowed to recover for 4 days (D8). Circulating plasma exosomes were isolated and incubated with human endothelial monolayer cultures for impedance measurements and RNA extracted and processed with messenger RNA (mRNA) arrays to identify gene targets. In addition, immunofluorescent assessments of endothelial nitric oxide synthase (eNOS) mRNA expression, ICAM-1 cellular distribution were conducted. Results: Plasma exosomal micro RNAs (miRNAs) were profiled. D4 exosomes, primarily from endothelial sources, disrupted impedance levels compared to D0 and D8. ICAM-1 expression was markedly upregulated in endothelial cells exposed to D4 exosomes along with significant reductions in eNOS expression. Microarray approaches identified a restricted and further validated signature of exosomal miRNAs in D4 exosomes, and mRNA arrays revealed putative endothelial gene target pathways. Conclusions:In humans, intermittent hypoxia alters exosome cargo in the circulation which promotes increased permeability and dysfunction of endothelial cells in vitro. A select number of circulating exosomal miRNAs may play important roles in the cardiovascular dysfunction associated with OSA by targeting specific effector pathways.

show abstract

“…There is also experimental and clinical evidence that genetic absence or functional inhibition of CD59 is a risk factor for vascular and neuropathic disease (An et al, 2009; Emin et al, 2016; Ghosh et al, 2013; Liu et al, 2014; Nevo et al, 2013; Qin et al, 2004; Wu et al, 2009; Yamashina et al, 1990; Yun et al, 2008). …”

Section: Introductionmentioning

confidence: 99%

Deficiency of the complement regulatory protein CD59 accelerates the development of diabetes-induced atherosclerosis in mice

Liu

Sahoo

et al. 2017

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

Aims Clinical and experimental evidence supports a strong link between the complement system, complement regulatory proteins and the pathogenesis of diabetes vascular complications. We previously reported that the complement regulatory protein CD59 is inactivated by glycation in humans with diabetes. Our objective for this study is to assess experimentally how the deficiency of CD59 impacts the development of diabetic atherosclerosis in vivo. Methods We crossed mCD59 sufficient and deficient mice into the ApoE−/− background to generate mCd59ab+/+/ApoE−/− and mCd59ab−/−/ApoE−/− mice, and induced diabetes by multiple low dose injections of streptozotocin. Atherosclerosis was detected by hematoxylin and eosin (H&E) and oil red-O staining. Membrane attack complex (MAC) deposition and macrophage infiltration were detected by immunostaining. Results Diabetic mCD59 deficient (mCD59ab−/−/ApoE−/−) mice developed nearly 100% larger atherosclerotic lesion areas in the aorta (7.5% ± 0.6 vs 3.6% ± 0.7; p < 0.005) and in the aortic roots (H&E: 26.2% ± 1.9 vs. 14.3% ± 1.1; p < 0.005), in both cases associated with increased lipid (Oil red-O: 14.9% ± 1.1 vs. 7.8% ± 1.1; p < 0.05) and MAC deposition (6.8% ± 0.8 vs. 3.0% ± 0.7; p <0.005) and macrophage infiltration (31.5% ± 3.7 vs. 16.4% ± 3.0; p <0.05) in the aortic roots as compared to their diabetic mCD59 sufficient (mCD59ab+/+/ApoE−/−) counterpart. Conclusions The deficiency of CD59 accelerates the development of diabetic atherosclerosis.

show abstract

Increased internalization of complement inhibitor CD59 may contribute to endothelial inflammation in obstructive sleep apnea

Cited by 40 publications

References 49 publications

Complement system activation in obstructive sleep apnea

Complement system activation in obstructive sleep apnea

Effect on Intermittent Hypoxia on Plasma Exosomal Micro RNA Signature and Endothelial Function in Healthy Adults

Deficiency of the complement regulatory protein CD59 accelerates the development of diabetes-induced atherosclerosis in mice

Contact Info

Product

Resources

About