Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
December-2021 Volume 22 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2021 Volume 22 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway

  • Authors:
    • Wenxun Liu
    • Yan Li
    • Zhaozhao Wu
    • Kerong Hai
    • Yun Wang
    • Xiaohong Zhou
    • Qingshan Ye
  • View Affiliations / Copyright

    Affiliations: Anesthesia Specialty, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Anesthesiology, Northwest Minzu University, Lanzhou, Gansu 730030, P.R. China, Department of Anesthesiology, People's Hospital of Ningxia Hui Autonomous Region, Yinchuan, Ningxia 750002, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 1397
    |
    Published online on: October 1, 2021
       https://doi.org/10.3892/etm.2021.10833
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Heparin is a commonly used in the clinic, however, Heparin's effect on endothelial injury remains unclear. The aim of the present study was to evaluate the effects and possible mechanisms of action underlying heparin treatment in lipopolysaccharide (LPS)‑induced endothelial injury in vitro. TNF‑α, IL‑1β, IL‑6 and IFN‑γ levels were measured using ELISA. Cell proliferation was measured using a 5‑ethynyl‑2'‑deoxyuridine (EdU) assay. The number of apoptotic cells and apoptotic rate were evaluated using TUNEL assays and flow cytometry, respectively. Toll‑like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88) and NF‑κB (p65) gene expression was evaluated using reverse transcription‑quantitative PCR, whilst TLR4, MyD88 and p‑NF‑κB (p65) protein expression was evaluated using western blot analysis. The levels of phosphorylated NF‑κB in the nucleus were evaluated using cellular immunofluorescence. Compared with those in the normal control group, TNF‑α, IL‑1β, IL‑6 and IFN‑γ levels were significantly increased in the LPS group (P<0.001). In addition, 5‑ethynyl‑2'‑deoxyuridine (EdU)‑positive cells were significantly increased and apoptosis was significantly decreased (P<0.001). TLR4, MyD88 and NF‑κB (p65) expression was also significantly increased (P<0.001). Compared with those in the LPS group, following heparin treatment, TNF‑α, IL‑1β, IL‑6 and IFN‑γ levels were significantly decreased (P<0.05), whilst the number of EdU‑positive cells was significantly increased and the level of apoptosis was significantly decreased (P<0.05). TLR4, MyD88 and NF‑κB (p65) expression was also significantly decreased by heparin in a dose‑dependent manner (P<0.001). Small interfering RNA‑TLR4 transfection exerted similar effects to those mediated by heparin in alleviating endothelial injury. In conclusion, heparin suppressed LPS‑induced endothelial injury through the regulation of TLR4/MyD88/NF‑κB (p65) signaling in vitro.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Figure 9

Figure 10

View References

1 

Stanhewicz AE, Wenner MM and Stachenfeld NS: Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan. Am J Physiol Heart Circ Physiol. 315:H1569–H1588. 2018.PubMed/NCBI View Article : Google Scholar

2 

Widlansky ME, Gokce N, Keaney JF Jr and Vita JA: The clinical implication of endothelial dysfunction. J Am Coll Cardiol. 42:1149–1160. 2003.PubMed/NCBI View Article : Google Scholar

3 

Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G and Nishigaki I: The vascular endothelium and human diseases. Int J Biol Sci. 9:1057–1069. 2013.PubMed/NCBI View Article : Google Scholar

4 

Sturtzel C: Endothelial cells. Adv Exp Med Biol. 1003:71–91. 2007.PubMed/NCBI View Article : Google Scholar

5 

Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, et al: Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol Feb. 14:249–256. 2012.PubMed/NCBI View Article : Google Scholar

6 

Huang AL and Vita JA: Effects of systemic inflammation on endothelium dependent vasodilation. Trends Cardiovasc Med. 16:15–20. 2006.PubMed/NCBI View Article : Google Scholar

7 

Kolluru GK, Bir SC and Kevil CG: Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med. 2012(918267)2012.PubMed/NCBI View Article : Google Scholar

8 

Park KH and Park WJ: Endothelial dysfunction: Clinical implication in cardiovascular disease and therapeutic approaches. J Korean Med Sci. 30:1213–1225. 2015.PubMed/NCBI View Article : Google Scholar

9 

Zhong L, Simard MJ and Huot J: Endothelial microRNAs regulating the NF-κB pathway and cell adhesion molecules during inflammation. FASEB J. 32:4070–4084. 2018.PubMed/NCBI View Article : Google Scholar

10 

Onishi A, St Ange K, Dordick JS and Linhardt RJ: Heparin and anticoagulation. Front Biosci (Landmark Ed). 21:1372–1392. 2016.PubMed/NCBI View Article : Google Scholar

11 

Ong CS, Marcum JA, Zehr KJ and Cameron DE: A century of heparin. Ann Thorac Surg. 108:955–958. 2019.PubMed/NCBI View Article : Google Scholar

12 

McLaughlin K, Nadeem L, Wat J, Baczyk D, Lye SJ and Kingdom JC: Low molecular weight heparin promotes transcription and release of placental growth factor from endothelial cells. Am J Physiol Heart Circ Physiol. 318:H1008–H1017. 2019.PubMed/NCBI View Article : Google Scholar

13 

Chen J, Wang H, Gao C, Liu D, Fan Y, Li W, Chen Y and Pan S: Tetramethylpyrazine alleviates LPS-induced inflammatory injury in HUVECs by inhibiting Rho/ROCK pathway. Biochem Biophys Res Commun. 514:329–335. 2019.PubMed/NCBI View Article : Google Scholar

14 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

15 

Haarmann R, Ibrahim M, Stevanovic M, Bredemeier R and Schleiff E: The properties of the outer membrane localized Lipid A transporter LptD. J Phys Condens Matter. 22(454124)2010.PubMed/NCBI View Article : Google Scholar

16 

Wan X, Wang PX, Zhou L and Xiang Q: Gene expression of toll-like receptors in the liver, lungs and spleen in mice after endotoxin challenge. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 16:73–76. 2004.PubMed/NCBI(In Chinese).

17 

Zhang J, Zheng Y, Luo Y, Du Y, Zhang X and Fu J: Curcumin inhibits LPS-induced neuroinflammation by promoting microglial M2 polarization via TREM2/ TLR4/ NF-κB pathways in BV2 cells. Mol Immunol. 116:29–37. 2019.PubMed/NCBI View Article : Google Scholar

18 

Xiao Q, Zhu X, Yang S, Wang J, Yin R, Song J, Ma A and Pan X: LPS induces CXCL16 expression in HUVECs through the miR-146a-mediated TLR4 pathway. Int Immunopharmacol. 69:143–149. 2019.PubMed/NCBI View Article : Google Scholar

19 

Li Y, Zhu H, Wei X, Li H, Yu Z, Zhang H and Liu W: LPS induces HUVEC angiogenesis in vitro through miR-146a-mediated TGF-β1 inhibition. Am J Transl Res. 15:591–600. 2017.PubMed/NCBI

20 

Cox D, Kerrigan SW and Watson SP: Platelets and the innate immune system: Mechanisms of bacterial-induced platelet activation. J Thromb Haemost. 9:1097–1107. 2011.PubMed/NCBI View Article : Google Scholar

21 

Cheng X, Yang YL, Yang H, Wang YH and Du GH: Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway. Int Immunopharmacol. 6:29–35. 2018.PubMed/NCBI View Article : Google Scholar

22 

Gu J, Su S, Guo J, Zhu Y, Zhao M and Duan JA: Anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae against focal cerebral ischaemia via TLR4/MyD88/MAPK/NF-κB signalling pathway in MCAO rats. J Pharm Pharmacol. 70:268–277. 2018.PubMed/NCBI View Article : Google Scholar

23 

Li C, Ai G, Wang Y, Lu Q, Luo C, Tan L, Lin G, Liu Y, Li Y, Zeng H, et al: Oxyberberine, a novel gut microbiota-mediated metabolite of berberine, possesses superior anti-colitis effect: Impact on intestinal epithelial barrier, gut microbiota profile and TLR4-MyD88-NF-κB pathway. Pharmacol Res. 152(104603)2020.PubMed/NCBI View Article : Google Scholar

24 

Li H, Zhong X, Li W and Wang Q: Effects of 1,25-dihydroxyvitamin D3 on experimental periodontitis and AhR/NF-κB/NLRP3 inflammasome pathway in a mouse model. J Appl Oral Sci. 27(e20180713)2019.PubMed/NCBI View Article : Google Scholar

25 

Kim SY, Jin CY, Kim CH, Yoo YH, Choi SH, Kim GY, Yoon HM, Park HT and Choi YH: Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation. Int J Mol Med. 43:682–692. 2019.PubMed/NCBI View Article : Google Scholar

26 

Kim DC, Quang TH, Oh H and Kim YC: Steppogenin isolated from Cudrania tricuspidata shows Antineuroinflammatory effects via NF-κB and MAPK pathways in LPS-Stimulated BV2 and primary rat microglial cells. Molecules. 22(2130)2017.PubMed/NCBI View Article : Google Scholar

27 

Yu X, Lan P, Hou X, Han Q, Lu N, Li T, Jiao C, Zhang J, Zhang C and Tian Z: HBV inhibits LPS-induced NLRP3 inflammasome activation and IL-1β production via suppressing the NF-κB pathway and ROS production. J Hepatol. 66:693–702. 2017.PubMed/NCBI View Article : Google Scholar

28 

Kauppinen A, Suuronen T, Ojala J, Kaarniranta K and Salminen A: Antagonistic crosstalk between NF-κB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal. 25:1939–1948. 2013.PubMed/NCBI View Article : Google Scholar

29 

Pober JS and Sessa WC: Evolving functions of endothelial cells in inflammation. Nature Rev Immunol. 7:803–815. 2007.PubMed/NCBI View Article : Google Scholar

30 

Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L and Giorgino F: Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases. Vascul Pharmacol. 100:1–19. 2018.PubMed/NCBI View Article : Google Scholar

31 

Bischoff J: Endothelial-to-mesenchymal transition. Circ Res. 124:1163–1165. 2019.PubMed/NCBI View Article : Google Scholar

32 

Deanfield JE, Halcox JP and Rabelink TJ: Endothelial function and dysfunction: Testing and clinical relevance. Circulation. 115:1285–1295. 2007.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu W, Li Y, Wu Z, Hai K, Wang Y, Zhou X and Ye Q: Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway. Exp Ther Med 22: 1397, 2021.
APA
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., & Ye, Q. (2021). Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway. Experimental and Therapeutic Medicine, 22, 1397. https://doi.org/10.3892/etm.2021.10833
MLA
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., Ye, Q."Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway". Experimental and Therapeutic Medicine 22.6 (2021): 1397.
Chicago
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., Ye, Q."Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1397. https://doi.org/10.3892/etm.2021.10833
Copy and paste a formatted citation
x
Spandidos Publications style
Liu W, Li Y, Wu Z, Hai K, Wang Y, Zhou X and Ye Q: Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway. Exp Ther Med 22: 1397, 2021.
APA
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., & Ye, Q. (2021). Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway. Experimental and Therapeutic Medicine, 22, 1397. https://doi.org/10.3892/etm.2021.10833
MLA
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., Ye, Q."Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway". Experimental and Therapeutic Medicine 22.6 (2021): 1397.
Chicago
Liu, W., Li, Y., Wu, Z., Hai, K., Wang, Y., Zhou, X., Ye, Q."Heparin alleviates LPS‑induced endothelial injury by regulating the TLR4/MyD88 signaling pathway". Experimental and Therapeutic Medicine 22, no. 6 (2021): 1397. https://doi.org/10.3892/etm.2021.10833
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team