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Published in: Sleep and Breathing 3/2018

01-09-2018 | Hypoxia • Original Article

dl-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress

Authors: Xiufang Zhou, Si Tang, Ke Hu, Zhan Zhang, Pei Liu, Yuchuan Luo, Jing Kang, Lifang Xu

Published in: Sleep and Breathing | Issue 3/2018

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Abstract

Background

Chronic intermittent hypoxia (CIH), an important basis of the pathogenesis of organ damage induced by obstructive sleep apnea syndrome (OSAS), is associated with myocardial injury, such as left ventricular dysfunction, apoptosis, and oxidative stress. Endogenous hydrogen sulfide (H2S) plays an important role in maintaining cardiovascular functions. Many studies have demonstrated that exogenous H2S has protective effects against myocardial injury induced by various cardiovascular diseases, and inhibiting the generation of endogenous H2S has opposite effects. However, the effect of dl-propargylglycine (PAG), an effective inhibitor of cystathionine γ-lyase (CSE)-synthesized H2S, on the regulation myocardial injury remains controversial.

Purpose

The present study was aimed to explore the influence of PAG on myocardial injury induced in rats by CIH.

Methods

Sprague-Dawley rats were randomly divided into a normal control (NC) group, a CIH group, a NC + PAG group, and a CIH + PAG group. After establishing the CIH model in rats, blood pressure, left ventricular function, oxidative stress, apoptosis, and the level of endoplasmic reticulum (ER) stress were detected.

Results

In NC rats, PAG had no effect on blood pressure, but induced myocardial dysfunction and up-regulated oxidative stress and apoptosis of the myocardium. In the CIH + PAG group, pretreatment with PAG significantly reduced blood pressure and improved the left ventricular ejection fraction (LVEF) and the left ventricular fractional shortening (LVFS) compared to the CIH group. Significantly lower levels of oxidative stress, apoptosis, and the ER stress were detected in the CIH + PAG group than in the CIH group.

Conclusion

These results suggest that PAG can protect the myocardium against CIH-induced injury through inhibition of endoplasmic reticulum stress.
Literature
5.
go back to reference Theodoropoulos K, Lykouras D, Karkoulias K, Damania D, Leou K, Lagiou O, Meelu OA, Rigopoulou A, Dangas GD, Hahalis G, Spiropoulos K, Starakis I (2017) Association between the severity of newly diagnosed obstructive sleep apnea and subclinical carotid atherosclerosis in patients without overt cardiovascular disease. European Rev Medical Pharmacological Sci 21(7):1568–1575 Theodoropoulos K, Lykouras D, Karkoulias K, Damania D, Leou K, Lagiou O, Meelu OA, Rigopoulou A, Dangas GD, Hahalis G, Spiropoulos K, Starakis I (2017) Association between the severity of newly diagnosed obstructive sleep apnea and subclinical carotid atherosclerosis in patients without overt cardiovascular disease. European Rev Medical Pharmacological Sci 21(7):1568–1575
11.
go back to reference Burguera EF, Meijide-Failde R, Blanco FJ (2016) Hydrogen sulfide and inflammatory joint diseases. Curr Drug Targets Burguera EF, Meijide-Failde R, Blanco FJ (2016) Hydrogen sulfide and inflammatory joint diseases. Curr Drug Targets
20.
go back to reference Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J (2009) Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S. J Biol Chem 284(5):3076–3085. https://doi.org/10.1074/jbc.M805459200 CrossRefPubMed Sun Q, Collins R, Huang S, Holmberg-Schiavone L, Anand GS, Tan CH, van-den-Berg S, Deng LW, Moore PK, Karlberg T, Sivaraman J (2009) Structural basis for the inhibition mechanism of human cystathionine gamma-lyase, an enzyme responsible for the production of H(2)S. J Biol Chem 284(5):3076–3085. https://​doi.​org/​10.​1074/​jbc.​M805459200 CrossRefPubMed
23.
go back to reference Oosterhuis NR, Frenay AR, Wesseling S, Snijder PM, Slaats GG, Yazdani S, Fernandez BO, Feelisch M, Giles RH, Verhaar MC, Joles JA, van Goor H (2015) DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats. Nitric Oxide : Biology Chemistry / Official J Nitric Oxide Soc 49:56–66. https://doi.org/10.1016/j.niox.2015.07.001 CrossRef Oosterhuis NR, Frenay AR, Wesseling S, Snijder PM, Slaats GG, Yazdani S, Fernandez BO, Feelisch M, Giles RH, Verhaar MC, Joles JA, van Goor H (2015) DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats. Nitric Oxide : Biology Chemistry / Official J Nitric Oxide Soc 49:56–66. https://​doi.​org/​10.​1016/​j.​niox.​2015.​07.​001 CrossRef
31.
go back to reference Liu YF, Chu YY, Zhang XZ, Zhang M, Xie FG, Zhou M, Wen HH, Shu AH (2017) TGFbeta1 protects myocardium from apoptosis and oxidative damage after ischemia reperfusion. European Rev Medical Pharmacological Sci 21(7):1551–1558 Liu YF, Chu YY, Zhang XZ, Zhang M, Xie FG, Zhou M, Wen HH, Shu AH (2017) TGFbeta1 protects myocardium from apoptosis and oxidative damage after ischemia reperfusion. European Rev Medical Pharmacological Sci 21(7):1551–1558
33.
go back to reference Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev 7(1):35–51CrossRefPubMed Lavie L (2003) Obstructive sleep apnoea syndrome—an oxidative stress disorder. Sleep Med Rev 7(1):35–51CrossRefPubMed
37.
go back to reference Inamoto S, Yoshioka T, Yamashita C, Miyamura M, Mori T, Ukimura A, Matsumoto C, Matsumura Y, Kitaura Y, Hayashi T (2010) Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice. Hypertension Res : Official J Japanese Soc Hypertension 33(6):579–586. https://doi.org/10.1038/hr.2010.36 CrossRef Inamoto S, Yoshioka T, Yamashita C, Miyamura M, Mori T, Ukimura A, Matsumoto C, Matsumura Y, Kitaura Y, Hayashi T (2010) Pitavastatin reduces oxidative stress and attenuates intermittent hypoxia-induced left ventricular remodeling in lean mice. Hypertension Res : Official J Japanese Soc Hypertension 33(6):579–586. https://​doi.​org/​10.​1038/​hr.​2010.​36 CrossRef
39.
go back to reference Nguyen M, Breckenridge DG, Ducret A, Shore GC (2000) Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria. Mol Cell Biol 20(18):6731–6740CrossRefPubMedPubMedCentral Nguyen M, Breckenridge DG, Ducret A, Shore GC (2000) Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria. Mol Cell Biol 20(18):6731–6740CrossRefPubMedPubMedCentral
42.
go back to reference Belaidi E, Thomas A, Bourdier G, Moulin S, Lemarie E, Levy P, Pepin JL, Korichneva I, Godin-Ribuot D, Arnaud C (2016) Endoplasmic reticulum stress as a novel inducer of hypoxia inducible factor-1 activity: its role in the susceptibility to myocardial ischemia-reperfusion induced by chronic intermittent hypoxia. Int J Cardiol 210:45–53. https://doi.org/10.1016/j.ijcard.2016.02.096 CrossRefPubMed Belaidi E, Thomas A, Bourdier G, Moulin S, Lemarie E, Levy P, Pepin JL, Korichneva I, Godin-Ribuot D, Arnaud C (2016) Endoplasmic reticulum stress as a novel inducer of hypoxia inducible factor-1 activity: its role in the susceptibility to myocardial ischemia-reperfusion induced by chronic intermittent hypoxia. Int J Cardiol 210:45–53. https://​doi.​org/​10.​1016/​j.​ijcard.​2016.​02.​096 CrossRefPubMed
43.
go back to reference Bos EM, Wang R, Snijder PM, Boersema M, Damman J, Fu M, Moser J, Hillebrands JL, Ploeg RJ, Yang G, Leuvenink HG, van Goor H (2013) Cystathionine gamma-lyase protects against renal ischemia/reperfusion by modulating oxidative stress. J Am Soc Nephrology : JASN 24 (5):759–770. doi:https://doi.org/10.1681/asn.2012030268 Bos EM, Wang R, Snijder PM, Boersema M, Damman J, Fu M, Moser J, Hillebrands JL, Ploeg RJ, Yang G, Leuvenink HG, van Goor H (2013) Cystathionine gamma-lyase protects against renal ischemia/reperfusion by modulating oxidative stress. J Am Soc Nephrology : JASN 24 (5):759–770. doi:https://​doi.​org/​10.​1681/​asn.​2012030268
Metadata
Title
dl-Propargylglycine protects against myocardial injury induced by chronic intermittent hypoxia through inhibition of endoplasmic reticulum stress
Authors
Xiufang Zhou
Si Tang
Ke Hu
Zhan Zhang
Pei Liu
Yuchuan Luo
Jing Kang
Lifang Xu
Publication date
01-09-2018
Publisher
Springer International Publishing
Published in
Sleep and Breathing / Issue 3/2018
Print ISSN: 1520-9512
Electronic ISSN: 1522-1709
DOI
https://doi.org/10.1007/s11325-018-1656-0

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