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Published in: Sleep and Breathing 1/2016

01-03-2016 | Original Article

Delayed neutrophil apoptosis mediates intermittent hypoxia-induced progressive heart failure in pressure-overloaded rats

Authors: Shuo Li, Jing Feng, Si Wei, Xuehan Qian, Jie Cao, Baoyuan Chen

Published in: Sleep and Breathing | Issue 1/2016

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Abstract

Background and objective

Obstructive sleep apnea (OSA) and heart failure (HF) are common coexisting diseases. Intermittent hypoxia (IH), caused by repeated apnea/hypopnea events, accompanied by increased systemic inflammation, might contribute to the promotion of HF.

Methods

To assess the hypothesis, rats were exposed to IH or normal air condition 4 weeks on the basis of normal heart function or pre-existing HF, which was induced by pressure overload caused by abdominal aortic constriction surgery performed 12 weeks earlier. Echocardiography was performed before and after IH exposure to evaluate left ventricular (LV) function. Serum concentrations of pro-inflammatory cytokines TNF-α and IL-6 were detected by enzyme-linked immunosorbent assay. Flow cytometric analysis was used to determine the apoptotic rate of polymorphonuclear neutrophils (PMNs).

Results

The echocardiographic study showed a significant decrease in LV fractional shortening (FS) and ejection fraction (EF) as well as an increase in the LV relative wall thickness (RWT) index in HF rats, which was aggravated by further exposure to IH compared with single-handed HF-only and sham-IH and sham-control groups. A reduced PMN apoptotic rate was observed in HF-IH rats compared with HF-only, sham-IH, and sham-control rats. Serum concentrations of TNF-α and IL-6 were also increased in HF-IH rats, accompanied by delayed PMN apoptosis, indicating significant systemic inflammation induced by IH.

Conclusion

The results of this study demonstrated that IH aggravates LV remodeling and heart dysfunction in rats with pre-existing HF. Delayed neutrophil apoptosis, which was revealed in HF rats following exposure to IH, contributed to the exacerbation of myocardial damage and progression of heart dysfunction.
Literature
1.
go back to reference Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365(9464):1046–1053CrossRefPubMed Marin JM, Carrizo SJ, Vicente E et al (2005) Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet 365(9464):1046–1053CrossRefPubMed
2.
go back to reference Shahar E, Whitney CW, Redline S et al (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163(1):19–25CrossRefPubMed Shahar E, Whitney CW, Redline S et al (2001) Sleep-disordered breathing and cardiovascular disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care Med 163(1):19–25CrossRefPubMed
3.
go back to reference Young T, Finn L, Peppard PE et al (2008) Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 31(8):1071–1078PubMedPubMedCentral Young T, Finn L, Peppard PE et al (2008) Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep 31(8):1071–1078PubMedPubMedCentral
4.
go back to reference Yumino D, Wang H, Floras JS et al (2009) Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail 15(4):279–285CrossRefPubMed Yumino D, Wang H, Floras JS et al (2009) Prevalence and physiological predictors of sleep apnea in patients with heart failure and systolic dysfunction. J Card Fail 15(4):279–285CrossRefPubMed
5.
go back to reference Ferrier K, Campbell A, Yee B et al (2005) Sleep-disordered breathing occurs frequently in stable outpatients with congestive heart failure. Chest 128(4):2116–2122CrossRefPubMed Ferrier K, Campbell A, Yee B et al (2005) Sleep-disordered breathing occurs frequently in stable outpatients with congestive heart failure. Chest 128(4):2116–2122CrossRefPubMed
6.
go back to reference Vazir A, Hastings PC, Dayer M et al (2007) A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail 9(3):243–250CrossRefPubMed Vazir A, Hastings PC, Dayer M et al (2007) A high prevalence of sleep disordered breathing in men with mild symptomatic chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail 9(3):243–250CrossRefPubMed
7.
go back to reference Garlichs CD, Eskafi S, Cicha I et al (2004) Delay of neutrophil apoptosis in acute coronary syndromes. J Leukoc Biol 75(5):828–835CrossRefPubMed Garlichs CD, Eskafi S, Cicha I et al (2004) Delay of neutrophil apoptosis in acute coronary syndromes. J Leukoc Biol 75(5):828–835CrossRefPubMed
8.
go back to reference Biasucci LM, Liuzzo G, Giubilato S et al (2009) Delayed neutrophil apoptosis in patients with unstable angina: relation to C-reactive protein and recurrence of instability. Eur Heart J 30(18):2220–2225CrossRefPubMed Biasucci LM, Liuzzo G, Giubilato S et al (2009) Delayed neutrophil apoptosis in patients with unstable angina: relation to C-reactive protein and recurrence of instability. Eur Heart J 30(18):2220–2225CrossRefPubMed
9.
go back to reference Dyugovskaya L, Polyakov A, Lavie P et al (2008) Delayed neutrophil apoptosis in patients with sleep apnea. Am J Respir Crit Care Med 177(5):544–554CrossRefPubMed Dyugovskaya L, Polyakov A, Lavie P et al (2008) Delayed neutrophil apoptosis in patients with sleep apnea. Am J Respir Crit Care Med 177(5):544–554CrossRefPubMed
10.
go back to reference Gomes AC, Falcao-Pires I, Pires AL et al (2013) Rodent models of heart failure: an updated review. Heart Fail Rev 18(2):219–249CrossRefPubMed Gomes AC, Falcao-Pires I, Pires AL et al (2013) Rodent models of heart failure: an updated review. Heart Fail Rev 18(2):219–249CrossRefPubMed
11.
go back to reference Xu XB, Pang JJ, Cao JM et al (2005) GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure. Am J Physiol Heart Circ Physiol 289(4):H1643–H1651CrossRefPubMed Xu XB, Pang JJ, Cao JM et al (2005) GH-releasing peptides improve cardiac dysfunction and cachexia and suppress stress-related hormones and cardiomyocyte apoptosis in rats with heart failure. Am J Physiol Heart Circ Physiol 289(4):H1643–H1651CrossRefPubMed
12.
go back to reference Chung ES, Perlini S, Aurigemma GP et al (1998) Effects of chronic adenosine uptake blockade on adrenergic responsiveness and left ventricular chamber function in pressure overload hypertrophy in the rat. J Hypertens 16(12 Pt 1):1813–1822CrossRefPubMed Chung ES, Perlini S, Aurigemma GP et al (1998) Effects of chronic adenosine uptake blockade on adrenergic responsiveness and left ventricular chamber function in pressure overload hypertrophy in the rat. J Hypertens 16(12 Pt 1):1813–1822CrossRefPubMed
13.
go back to reference Feng J, Chen BY, Cui LY et al (2009) Inflammation status of rabbit carotid artery model endothelium during intermittent hypoxia exposure and its relationship with leptin. Sleep Breath 13(3):277–283CrossRefPubMed Feng J, Chen BY, Cui LY et al (2009) Inflammation status of rabbit carotid artery model endothelium during intermittent hypoxia exposure and its relationship with leptin. Sleep Breath 13(3):277–283CrossRefPubMed
14.
go back to reference Feng J, Wang QS, Chiang A et al (2010) The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats. PLoS ONE 5(10):e13201CrossRefPubMedPubMedCentral Feng J, Wang QS, Chiang A et al (2010) The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats. PLoS ONE 5(10):e13201CrossRefPubMedPubMedCentral
15.
go back to reference Teichholz LE, Kreulen T, Herman MV et al (1976) Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37(1):7–11CrossRefPubMed Teichholz LE, Kreulen T, Herman MV et al (1976) Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol 37(1):7–11CrossRefPubMed
16.
go back to reference Tidholm A, Westling AB, Hoglund K et al (2010) Comparisons of 3-, 2-dimensional, and M-mode echocardiographical methods for estimation of left chamber volumes in dogs with and without acquired heart disease. J Vet Intern Med 24(6):1414–1420CrossRefPubMed Tidholm A, Westling AB, Hoglund K et al (2010) Comparisons of 3-, 2-dimensional, and M-mode echocardiographical methods for estimation of left chamber volumes in dogs with and without acquired heart disease. J Vet Intern Med 24(6):1414–1420CrossRefPubMed
17.
go back to reference Lang RM, Bierig M, Devereux RB et al (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108CrossRefPubMed Lang RM, Bierig M, Devereux RB et al (2006) Recommendations for chamber quantification. Eur J Echocardiogr 7(2):79–108CrossRefPubMed
18.
go back to reference da Silva MG, Mattos E, Camacho-Pereira J et al (2012) Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases. Exp Clin Cardiol 17(3):101–109PubMedPubMedCentral da Silva MG, Mattos E, Camacho-Pereira J et al (2012) Cardiac systolic dysfunction in doxorubicin-challenged rats is associated with upregulation of MuRF2 and MuRF3 E3 ligases. Exp Clin Cardiol 17(3):101–109PubMedPubMedCentral
19.
go back to reference Krumholz HM, Larson M, Levy D (1995) Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol 25(4):879–884CrossRefPubMed Krumholz HM, Larson M, Levy D (1995) Prognosis of left ventricular geometric patterns in the Framingham Heart Study. J Am Coll Cardiol 25(4):879–884CrossRefPubMed
20.
go back to reference Strober, W. (2001) Trypan blue exclusion test of cell viability. Curr Protoc Immunol; Appendix 3: Appendix 3B. Strober, W. (2001) Trypan blue exclusion test of cell viability. Curr Protoc Immunol; Appendix 3: Appendix 3B.
21.
go back to reference Vermes I, Haanen C, Steffens-Nakken H et al (1995) A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 184(1):39–51CrossRefPubMed Vermes I, Haanen C, Steffens-Nakken H et al (1995) A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods 184(1):39–51CrossRefPubMed
22.
go back to reference El Solh AA, Akinnusi ME, Baddoura FH et al (2007) Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. Am J Respir Crit Care Med 175(11):1186–1191CrossRefPubMed El Solh AA, Akinnusi ME, Baddoura FH et al (2007) Endothelial cell apoptosis in obstructive sleep apnea: a link to endothelial dysfunction. Am J Respir Crit Care Med 175(11):1186–1191CrossRefPubMed
23.
go back to reference Li S, Qian XH, Zhou W et al (2011) Time-dependent inflammatory factor production and NFkappaB activation in a rodent model of intermittent hypoxia. Swiss Med Wkly 141:w13309PubMed Li S, Qian XH, Zhou W et al (2011) Time-dependent inflammatory factor production and NFkappaB activation in a rodent model of intermittent hypoxia. Swiss Med Wkly 141:w13309PubMed
24.
go back to reference Egea CJ, Aizpuru F, Pinto JA et al (2008) Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Med 9(6):660–666CrossRefPubMed Egea CJ, Aizpuru F, Pinto JA et al (2008) Cardiac function after CPAP therapy in patients with chronic heart failure and sleep apnea: a multicenter study. Sleep Med 9(6):660–666CrossRefPubMed
25.
go back to reference Krieger J, Grucker D, Sforza E et al (1991) Left ventricular ejection fraction in obstructive sleep apnea. Effects of long-term treatment with nasal continuous positive airway pressure. Chest 100(4):917–921CrossRefPubMed Krieger J, Grucker D, Sforza E et al (1991) Left ventricular ejection fraction in obstructive sleep apnea. Effects of long-term treatment with nasal continuous positive airway pressure. Chest 100(4):917–921CrossRefPubMed
26.
go back to reference Cioffi G, Russo TE, Stefenelli C et al (2010) Severe obstructive sleep apnea elicits concentric left ventricular geometry. J Hypertens 28(5):1074–1082CrossRefPubMed Cioffi G, Russo TE, Stefenelli C et al (2010) Severe obstructive sleep apnea elicits concentric left ventricular geometry. J Hypertens 28(5):1074–1082CrossRefPubMed
27.
go back to reference Jimenez MF, Watson RW, Parodo J et al (1997) Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome. Arch Surg 132(12):1263–1269, discussion 9–70 CrossRefPubMed Jimenez MF, Watson RW, Parodo J et al (1997) Dysregulated expression of neutrophil apoptosis in the systemic inflammatory response syndrome. Arch Surg 132(12):1263–1269, discussion 9–70 CrossRefPubMed
28.
go back to reference Biffl WL, Moore EE, Moore FA et al (1996) Interleukin-6 delays neutrophil apoptosis. Arch Surg 131(1):24–29, discussion 9–30 CrossRefPubMed Biffl WL, Moore EE, Moore FA et al (1996) Interleukin-6 delays neutrophil apoptosis. Arch Surg 131(1):24–29, discussion 9–30 CrossRefPubMed
29.
go back to reference Matsuda T, Saito H, Fukatsu K et al (2001) Cytokine-modulated inhibition of neutrophil apoptosis at local site augments exudative neutrophil functions and reflects inflammatory response after surgery. Surgery 129(1):76–85CrossRefPubMed Matsuda T, Saito H, Fukatsu K et al (2001) Cytokine-modulated inhibition of neutrophil apoptosis at local site augments exudative neutrophil functions and reflects inflammatory response after surgery. Surgery 129(1):76–85CrossRefPubMed
30.
go back to reference Francois S, El Benna J, Dang PM et al (2005) Inhibition of neutrophil apoptosis by TLR agonists in whole blood: involvement of the phosphoinositide 3-kinase/Akt and NF-kappaB signaling pathways, leading to increased levels of Mcl-1, A1, and phosphorylated Bad. J Immunol 174(6):3633–3642CrossRefPubMed Francois S, El Benna J, Dang PM et al (2005) Inhibition of neutrophil apoptosis by TLR agonists in whole blood: involvement of the phosphoinositide 3-kinase/Akt and NF-kappaB signaling pathways, leading to increased levels of Mcl-1, A1, and phosphorylated Bad. J Immunol 174(6):3633–3642CrossRefPubMed
31.
go back to reference Beg AA, Baltimore D (1996) An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274(5288):782–784CrossRefPubMed Beg AA, Baltimore D (1996) An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science 274(5288):782–784CrossRefPubMed
32.
go back to reference Walmsley SR, Print C, Farahi N et al (2005) Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med 201(1):105–115CrossRefPubMedPubMedCentral Walmsley SR, Print C, Farahi N et al (2005) Hypoxia-induced neutrophil survival is mediated by HIF-1alpha-dependent NF-kappaB activity. J Exp Med 201(1):105–115CrossRefPubMedPubMedCentral
33.
go back to reference Choi M, Rolle S, Wellner M et al (2003) Inhibition of NF-kappaB by a TAT-NEMO-binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis. Blood 102(6):2259–2267CrossRefPubMed Choi M, Rolle S, Wellner M et al (2003) Inhibition of NF-kappaB by a TAT-NEMO-binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis. Blood 102(6):2259–2267CrossRefPubMed
Metadata
Title
Delayed neutrophil apoptosis mediates intermittent hypoxia-induced progressive heart failure in pressure-overloaded rats
Authors
Shuo Li
Jing Feng
Si Wei
Xuehan Qian
Jie Cao
Baoyuan Chen
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Sleep and Breathing / Issue 1/2016
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-015-1190-2

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