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Article

Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension

  • Authors:
    • Wencheng Yu
    • Xiaoxia Song
    • Chen Lin
    • Weina Ji
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Respiratory Medicine, Central Hospital of Shengli Oil Field, Dongying, Shandong 257000, P.R. China
  • Pages: 5503-5509
    |
    Published online on: April 27, 2018
       https://doi.org/10.3892/etm.2018.6103
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Abstract

The aim of the present study was to investigate the impact of N‑acetylcysteine (NAC) on the expression of activin receptor‑like kinase‑1 (ALK‑1) and mothers against decapentaplegic homolog 1 (Smad1) in the pulmonary artery of rats with pulmonary arterial hypertension (PAH), and to explore the possible mechanisms underlying its effects on pulmonary vascular remodeling (PVR). In total, 32 Wistar rats were randomly divided into four groups: Control, model, low‑dose (100 mg/kg/day) NAC and high‑dose (500 mg/kg/day) NAC. Monocrotaline (MCT) was intraperitoneally injected to prepare the model, and the right ventricular hypertrophy index (RVHI) and hemodynamic parameters were detected 6 weeks later. Hematoxylin and eosin staining was used to observe the pulmonary arterial structural changes and evaluate the peri‑pulmonary artery inflammation score. Additionally, western blot analysis was used to detect the protein expression of ALK‑1 and Smad1 in the pulmonary artery. The results demonstrated that treatment with NAC reduced RVHI and mean pulmonary artery pressure. In addition, NAC reduced the MCT‑induced PVR, pulmonary inflammation score and upregulation of ALK‑1 and Smad1. These results indicate that ALK‑1 and Smad1 participate in the formation of PAH and the process of PVR, and suggest that NAC may inhibit PAH by inhibiting the expression of ALK‑1 and Smad1 in the pulmonary artery.
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1 

Hecker M, Zaslona Z, Kwapiszewska G, Niess G, Zakrzewicz A, Hergenreider E, Wilhelm J, Marsh LM, Sedding D, Klepetko W, et al: Dysregulation of the IL-13 receptor system: A novel pathomechanism in pulmonary arterial hypertension. Am J Respir Crit Care Med. 182:805–818. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Galiè N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Noordegraaf Vonk A, Beghetti M, et al: 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J. 37:67–119. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Qiao S, Fan K, Iwashita T, Ichihara M, Yoshino M and Takahashi M: The involvement of reactive oxygen species derived from NADPH oxidase-1 activation on the constitutive tyrosine auto-phosphorylation of RET proteins. Free Radic Res. 48:427–434. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Schermuly RT, Ghofrani HA, Wilkins MR and Grimminger F: Mechanisms of disease: Pulmonary arterial hypertension. Nat Rev Cardiol. 8:443–455. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Cunha SI, Pardali E, Thorikay M, Anderberg C, Hawinkels L, Goumans MJ, Seehra J, Heldin CH, ten Dijke P and Pietras K: Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis. J Exp Med. 207:85–100. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Gore B, Izikki M, Mercier O, Dewachter L, Fadel E, Humbert M, Dartevelle P, Simonneau G, Naeije R, Lebrin F and Eddahibi S: Key role of the endothelial TGF-β/ALK1/endoglin signaling pathway in humans and rodents pulmonary hypertension. PLoS One. 9:e1003102014. View Article : Google Scholar : PubMed/NCBI

7 

Girerd B, Montani D, Coulet F, Sztrymf B, Yaici A, Jaïs X, Tregouet D, Reis A, Drouin-Garraud V, Fraisse A, et al: Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 181:851–861. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Goumans MJ, Liu Z and ten Dijke P: TGF-beta signaling in vascular biology and dysfunction. Cell Res. 19:116–127. 2009. View Article : Google Scholar : PubMed/NCBI

9 

López-Novoa JM and Bernabeu C: The physiological role of endoglin in the cardiovascular system. Am J Physiol Heart Circ Physiol. 299:H959–H974. 2010. View Article : Google Scholar : PubMed/NCBI

10 

Santibañez JF, Quintanilla M and Bernabeu C: TGF-β/TGF-β receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 121:233–251. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Albro MB, Nims RJ, Durney KM, Cigan AD, Shim JJ, Vunjak-Novakovic G, Hung CT and Ateshian GA: Heterogeneous engineered cartilage growth results from gradients of media-supplemented active TGF-β and is ameliorated by the alternative supplementation of latent TGF-β. Biomaterials. 77:173–185. 2016. View Article : Google Scholar : PubMed/NCBI

12 

López-Hernández FJ and López-Novoa JM: Role of TGF-β in chronic kidney disease: An integration of tubular, glomerular and vascular effects. Cell Tissue Res. 347:141–154. 2012. View Article : Google Scholar : PubMed/NCBI

13 

Tanjore H, Blackwell TS and Lawson WE: Emerging evidence for endoplasmic reticulum stress in the pathogenesis of idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 302:L721–L729. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Chaumais MC, Ranchoux B, Montani D, Dorfmüller P, Tu L, Lecerf F, Raymond N, Guignabert C, Price L, Simonneau G, et al: N-acetylcysteine improves established monocrotaline-induced pulmonary hypertension in rats. Respir Res. 15:652014. View Article : Google Scholar : PubMed/NCBI

15 

Idrees MM, Saleemi S, Azem MA, Aldammas S, Alhazmi M, Khan J, Gari A, Aldabbagh M, Sakkijha H, Aldalaan A, et al: Saudi guidelines on the diagnosis and treatment of pulmonary hypertension: 2014 updates. Ann Thorac Med. 9 Suppl 1:S1–S15. 2014. View Article : Google Scholar : PubMed/NCBI

16 

Yuan P, Wu WH, Liu D, Zhang R and Jing ZC: Determination of pulmonary vascular resistance by improved right heart catheter in rat. Zhonghua Xin Xue Guan Bing Za Zhi. 39:901–904. 2011.(In Chinese). PubMed/NCBI

17 

Good RB, Gilbane AJ, Trinder SL, Denton CP, Coghlan G, Abraham DJ and Holmes AM: Endothelial to mesenchymal transition contributes to endothelial dysfunction in pulmonary arterial hypertension. Am J Pathol. 185:1850–1858. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Evans JD, Girerd B, Montani D, Wang XJ, Galiè N, Austin ED, Elliott G, Asano K, Grünig E, Yan Y, et al: BMPR2 mutations and survival in pulmonary arterial hypertension: An individual participant data meta-analysis. Lancet Respir Med. 4:129–137. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Takahashi J, Orcholski M, Yuan K and de Jesus Perez V: PDGF-dependent β-catenin activation is associated with abnormal pulmonary artery smooth muscle cell proliferation in pulmonary arterial hypertension. FEBS Lett. 590:101–109. 2016. View Article : Google Scholar : PubMed/NCBI

20 

Sarrion I, Milian L, Juan G, Ramon M, Furest I, Carda C, Gimeno Cortijo J and Roig Mata M: Role of circulating miRNAs as biomarkers in idiopathic pulmonary arterial hypertension: Possible relevance of miR-23a. Oxid Med Cell Longev. 2015:7928462015. View Article : Google Scholar : PubMed/NCBI

21 

Cogan JD, Pauciulo MW, Batchman AP, Prince MA, Robbins IM, Hedges LK, Stanton KC, Wheeler LA, Phillips JA III, Loyd JE and Nichols WC: High frequency of BMPR2 exonic deletions/duplications in familial pulmonary arterial hypertension. Am J Respir Crit Care Med. 174:590–598. 2006. View Article : Google Scholar : PubMed/NCBI

22 

McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, et al: ACCF/AHA 2009 expert consensus document on pulmonary hypertension: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association: Developed in Collaboration With the American College of Chest Physicians, American Thoracic Society, Inc., and the Pulmonary Hypertension Association. Circulation. 119:2250–2294. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Morine KJ, Qiao X, Paruchuri V, Aronovitz MJ, Mackey EE, Buiten L, Levine J, Ughreja K, Nepali P, Blanton RM, et al: Conditional knockout of activin like kinase-1 (ALK-1) leads to heart failure without maladaptive remodeling. Heart Vessels. 32:628–636. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Mishra A, Stueckle TA, Mercer RR, Derk R, Rojanasakul Y, Castranova V and Wang L: Identification of TGF-β receptor-1 as a key regulator of carbon nanotube-induced fibrogenesis. Am J Physiol Lung Cell Mol Physiol. 309:L821–L833. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Mitchell D, Pobre EG, Mulivor AW, Grinberg AV, Castonguay R, Monnell TE, Solban N, Ucran JA, Pearsall RS, Underwood KW, et al: ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth. Mol Cancer Ther. 9:379–388. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Jerkic M, Kabir MG, Davies A, Yu LX, McIntyre BA, Husain NW, Enomoto M, Sotov V, Husain M, Henkelman M, et al: Pulmonary hypertension in adult Alk1 heterozygous mice due to oxidative stress. Cardiovasc Res. 92:375–384. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Eyries M, Coulet F, Girerd B, Montani D, Humbert M, Lacombe P, Chinet T, Gouya L, Roume J, Axford MM, et al: ACVRL1 germinal mosaic with two mutant alleles in hereditary hemorrhagic telangiectasia associated with pulmonary arterial hypertension. Clin Genet. 82:173–179. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Chen L, Xiao J, Li Y and Ma H: Ang-(1–7) might prevent the development of monocrotaline induced pulmonary arterial hypertension in rats. Eur Rev Med Pharmacol Sci. 15:1–7. 2011.PubMed/NCBI

29 

Xi Y, Tan K, Brumwell AN, Chen SC, Kim YH, Kim TJ, Wei Y and Chapman HA: Inhibition of epithelial-to-mesenchymal transition and pulmonary fibrosis by methacycline. Am J Respir Cell Mol Biol. 50:51–60. 2014.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yu W, Song X, Lin C and Ji W: Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension. Exp Ther Med 15: 5503-5509, 2018.
APA
Yu, W., Song, X., Lin, C., & Ji, W. (2018). Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension. Experimental and Therapeutic Medicine, 15, 5503-5509. https://doi.org/10.3892/etm.2018.6103
MLA
Yu, W., Song, X., Lin, C., Ji, W."Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension". Experimental and Therapeutic Medicine 15.6 (2018): 5503-5509.
Chicago
Yu, W., Song, X., Lin, C., Ji, W."Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension". Experimental and Therapeutic Medicine 15, no. 6 (2018): 5503-5509. https://doi.org/10.3892/etm.2018.6103
Copy and paste a formatted citation
x
Spandidos Publications style
Yu W, Song X, Lin C and Ji W: Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension. Exp Ther Med 15: 5503-5509, 2018.
APA
Yu, W., Song, X., Lin, C., & Ji, W. (2018). Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension. Experimental and Therapeutic Medicine, 15, 5503-5509. https://doi.org/10.3892/etm.2018.6103
MLA
Yu, W., Song, X., Lin, C., Ji, W."Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension". Experimental and Therapeutic Medicine 15.6 (2018): 5503-5509.
Chicago
Yu, W., Song, X., Lin, C., Ji, W."Interventions and mechanisms of N‑acetylcysteine on monocrotaline‑induced pulmonary arterial hypertension". Experimental and Therapeutic Medicine 15, no. 6 (2018): 5503-5509. https://doi.org/10.3892/etm.2018.6103
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