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
August-2021 Volume 22 Issue 2

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
August-2021 Volume 22 Issue 2

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

HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1

  • Authors:
    • Shilei Liu
    • Jing Gao
    • Sai Wang
  • View Affiliations / Copyright

    Affiliations: Internal Medicine‑Cardiovascular Department, Shengli Oilfield Central Hospital, Dongying, Shandong 257000, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Article Number: 871
    |
    Published online on: June 13, 2021
       https://doi.org/10.3892/etm.2021.10303
  • 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

Atherosclerosis (AS) is a chronic pathophysiological process that causes high mortality and morbidity. It has previously been reported that homeobox A9 (HOXA9) may participate in regulation of the cardiovascular system and the pathology of AS by upregulating E‑selectin and vascular cell adhesion molecule‑1 (VCAM‑1). Thus, inhibiting HOXA9 could promote microcirculation of coronary arteries and could act as a potential therapy for AS treatment. Sprague‑Dawley rats were randomly divided into four groups, as follows: i) AS; ii) AS + HOXA9 inhibitor; iii) AS + small interfering RNA‑HOXA9 and iv) normal control. ELISA was used to measure the levels of TNF‑α, IL‑1β, IL‑12, C‑C motif chemokine ligand 25 (CCL25), low‑density lipoprotein (LDL), high‑density lipoprotein (HDL) and very‑low‑density lipoprotein (VLDL). Flow cytometry was employed to detect the content of M1 macrophages. Hematoxylin & eosin (H&E) staining was performed to observe the morphology of the coronary arteries. Oil red O staining was conducted for the evaluation of lipid accumulation. Immunohistochemistry was used to visualize the protein expression levels of HOXA9 in the coronary arteries. Western blotting was utilized to determine the protein expression levels of HOXA9, platelet factor‑4 (PF4), E‑selectin and VCAM‑1. HOXA9 inhibitors were found to downregulate the levels of TNF‑α, IL‑1β, IL‑12, CCL25, LDL and VLDL, and upregulate HDL levels in the blood of AS rats. The content of M1 macrophages was also decreased following injection of HOXA9 inhibitors in the AS group. H&E and oil red O staining analysis indicated that HOXA9 inhibitors attenuated vascular symptoms and lipid formation in AS rats. Furthermore, western blotting suggested that inhibition of HOXA9 reduced the expression levels of PF4, E‑selectin and VCAM‑1, while overexpression of PF4 resulted in the opposite effects. The present study revealed that inhibiting HOXA9 alleviated the symptoms of AS via downregulation of the PF4 and E‑selectin/VCAM‑1 pathway to promote microcirculation in the coronary arteries of AS rats. These findings indicated that HOXA9 inhibitors may have the potential to succeed in the treatment of AS.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Libby P, Lichtman AH and Hansson GK: Immune effector mechanisms implicated in atherosclerosis: From mice to humans. Immunity. 38:1092–1104. 2013.PubMed/NCBI View Article : Google Scholar

2 

Kwon GP, Schroeder JL, Amar MJ, Remaley AT and Balaban RS: Contribution of macromolecular structure to the retention of low-density lipoprotein at arterial branch points. Circulation. 117:2919–2927. 2008.PubMed/NCBI View Article : Google Scholar

3 

Bäck M and Hansson GK: Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol. 12:199–211. 2015.PubMed/NCBI View Article : Google Scholar

4 

Herrero-Fernandez B, Gomez-Bris R, Somovilla-Crespo B and Gonzalez-Granado JM: Immunobiology of atherosclerosis: A complex net of interactions. Int J Mol Sci. 20(5293)2019.PubMed/NCBI View Article : Google Scholar

5 

Gimbrone MA Jr and García-Cardeña G: Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res. 118:620–636. 2016.PubMed/NCBI View Article : Google Scholar

6 

Barrett TJ: Macrophages in atherosclerosis regression. Arterioscler Thromb Vasc Biol. 40:20–33. 2020.PubMed/NCBI View Article : Google Scholar

7 

Chistiakov DA, Orekhov AN and Bobryshev YV: Endothelial barrier and its abnormalities in cardiovascular disease. Front Physiol. 6(365)2015.PubMed/NCBI View Article : Google Scholar

8 

Chistiakov DA, Melnichenko AA, Myasoedova VA, Grechko AV and Orekhov AN: Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl). 95:1153–1165. 2017.PubMed/NCBI View Article : Google Scholar

9 

Bakogiannis C, Sachse M, Stamatelopoulos K and Stellos K: Platelet-derived chemokines in inflammation and atherosclerosis. Cytokine. 122(154157)2019.PubMed/NCBI View Article : Google Scholar

10 

Iademarco MF, Barks JL and Dean DC: Regulation of vascular cell adhesion molecule-1 expression by IL-4 and TNF-alpha in cultured endothelial cells. J Clin Invest. 95:264–271. 1995.PubMed/NCBI View Article : Google Scholar

11 

Cantile M, Schiavo G, Terracciano L and Cillo C: Homeobox genes in normal and abnormal vasculogenesis. Nutr Metab Cardiovasc Dis. 18:651–658. 2008.PubMed/NCBI View Article : Google Scholar

12 

Duboule D and Morata G: Colinearity and functional hierarchy among genes of the homeotic complexes. Trends Genet. 10:358–364. 1994.PubMed/NCBI View Article : Google Scholar

13 

Gorski DH and Walsh K: The role of homeobox genes in vascular remodeling and angiogenesis. Circ Res. 87:865–872. 2000.PubMed/NCBI View Article : Google Scholar

14 

Bandyopadhyay S, Ashraf MZ, Daher P, Howe PH and DiCorleto PE: HOXA9 participates in the transcriptional activation of E-selectin in endothelial cells. Mol Cell Biol. 27:4207–4216. 2007.PubMed/NCBI View Article : Google Scholar

15 

Pang J, Xu Q, Xu X, Yin H, Xu R, Guo S, Hao W, Wang L, Chen C and Cao JM: Hexarelin suppresses high lipid diet and vitamin D3-induced atherosclerosis in the rat. Peptides. 31:630–638. 2010.PubMed/NCBI View Article : Google Scholar

16 

Zheng X and Hu X: Effects of rosuvastatin on hypertension with carotid atherosclerosis and its influence on peripheral macrophage polarization. Chinese Journal of Clinical Pharmacology and Therapeutics. 22:1035–1039. 2017.

17 

Wang J, Hou J, Lin C, Fu J, Ren J, Li L, Guo H, Han X, Wang B and Liu J: Shuangshen ningxin capsule, a traditional Chinese medicinal preparation, alleviates myocardial ischemia through autophagy regulation. Evid Based Complement Alternat Med. 2015(581260)2015.PubMed/NCBI View Article : Google Scholar

18 

Xu B, Geerts D, Bu Z, Ai J, Jin L, Li Y, Zhang H and Zhu G: Regulation of endometrial receptivity by the highly expressed HOXA9, HOXA11 and HOXD10 HOX-class homeobox genes. Hum Reprod. 29:781–790. 2014.PubMed/NCBI View Article : Google Scholar

19 

Sun X, He S, Wara AKM, Icli B, Shvartz E, Tesmenitsky Y, Belkin N, Li D, Blackwell TS, Sukhova GK, et al: Systemic delivery of microRNA-181b inhibits nuclear factor-κB activation, vascular inflammation, and atherosclerosis in apolipoprotein E-deficient mice. Circ Res. 114:32–40. 2014.PubMed/NCBI View Article : Google Scholar

20 

Shirai T, Hilhorst M, Harrison DG, Goronzy JJ and Weyand CM: Macrophages in vascular inflammation-From atherosclerosis to vasculitis. Autoimmunity. 48:139–151. 2015.PubMed/NCBI View Article : Google Scholar

21 

Nitsa A, Toutouza M, Machairas N, Mariolis A, Philippou A and Koutsilieris M: Vitamin D in cardiovascular disease. In Vivo. 32:977–981. 2018.PubMed/NCBI View Article : Google Scholar

22 

Xie W, Li L, Zhang M, Cheng HP, Gong D, Lv YC, Yao F, He PP, Ouyang XP, Lan G, et al: MicroRNA-27 prevents atherosclerosis by suppressing lipoprotein lipase-induced lipid accumulation and inflammatory response in apolipoprotein E knockout mice. PLoS One. 11(e0157085)2016.PubMed/NCBI View Article : Google Scholar

23 

Calvo KR, Sykes DB, Pasillas M and Kamps MP: Hoxa9 immortalizes a granulocyte-macrophage colony-stimulating factor-dependent promyelocyte capable of biphenotypic differentiation to neutrophils or macrophages, independent of enforced meis expression. Mol Cell Biol. 20:3274–3285. 2000.PubMed/NCBI View Article : Google Scholar

24 

Trivedi CM, Patel RC and Patel CV: Homeobox gene HOXA9 inhibits nuclear factor-kappa B dependent activation of endothelium. Atherosclerosis. 195:e50–e60. 2007.PubMed/NCBI View Article : Google Scholar

25 

Xuan W, Qu Q, Zheng B, Xiong S and Fan GH: The chemotaxis of M1 and M2 macrophages is regulated by different chemokines. J Leukoc Biol. 97:61–69. 2015.PubMed/NCBI View Article : Google Scholar

26 

Li W, Tang C, Jin H and Du J: Effects of onion extract on endogenous vascular H2S and adrenomedulin in rat atherosclerosis. Curr Pharm Biotechnol. 12:1427–1439. 2011.PubMed/NCBI View Article : Google Scholar

27 

Domschke G and Gleissner CA: CXCL4-induced macrophages in human atherosclerosis. Cytokine. 122(154141)2019.PubMed/NCBI View Article : Google Scholar

28 

Jiang Y, Jiang LL, Maimaitirexiati XM, Zhang Y and Wu L: Irbesartan attenuates TNF-α-induced ICAM-1, VCAM-1, and E-selectin expression through suppression of NF-κB pathway in HUVECs. Eur Rev Med Pharmacol Sci. 19:3295–3302. 2015.PubMed/NCBI

29 

Shih MF, Pan KH, Liu CC, Shen CR and Cherng JY: Treatment of β-thujaplicin counteracts di(2-ethylhexyl)phthalate (DEHP)-exposed vascular smooth muscle activation, inflammation and atherosclerosis progression. Regul Toxicol Pharmacol. 92:333–337. 2018.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu S, Gao J and Wang S: HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1. Exp Ther Med 22: 871, 2021.
APA
Liu, S., Gao, J., & Wang, S. (2021). HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1. Experimental and Therapeutic Medicine, 22, 871. https://doi.org/10.3892/etm.2021.10303
MLA
Liu, S., Gao, J., Wang, S."HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1". Experimental and Therapeutic Medicine 22.2 (2021): 871.
Chicago
Liu, S., Gao, J., Wang, S."HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1". Experimental and Therapeutic Medicine 22, no. 2 (2021): 871. https://doi.org/10.3892/etm.2021.10303
Copy and paste a formatted citation
x
Spandidos Publications style
Liu S, Gao J and Wang S: HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1. Exp Ther Med 22: 871, 2021.
APA
Liu, S., Gao, J., & Wang, S. (2021). HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1. Experimental and Therapeutic Medicine, 22, 871. https://doi.org/10.3892/etm.2021.10303
MLA
Liu, S., Gao, J., Wang, S."HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1". Experimental and Therapeutic Medicine 22.2 (2021): 871.
Chicago
Liu, S., Gao, J., Wang, S."HOXA9 inhibitors promote microcirculation of coronary arteries in rats via downregulating E‑selectin/VCAM‑1". Experimental and Therapeutic Medicine 22, no. 2 (2021): 871. https://doi.org/10.3892/etm.2021.10303
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