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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
January-2018 Volume 17 Issue 1

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
January-2018 Volume 17 Issue 1

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
Article Open Access

Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats

  • Authors:
    • Tingjun Wang
    • Guili Lian
    • Xiaoqi Cai
    • Zhihong Lin
    • Liangdi Xie
  • View Affiliations / Copyright

    Affiliations: Fujian Hypertension Research Institute, The First Clinical College of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1753-1761
    |
    Published online on: November 15, 2017
       https://doi.org/10.3892/mmr.2017.8081
  • 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

Hypertension is frequently associated with metabolic disorders. The present study was designed to investigate the long‑term effect of prehypertensive losartan therapy on metabolic disorders in high‑fat‑fed spontaneously hypertensive rats (SHRs), and to examine the role of epigenetic regulation of angiotensin II type 1 receptor (AT1R) and AT1 receptor‑associated protein (ATRAP) expression in adipose tissue. A total of 32 4‑week‑old male SHRs were divided into four groups (n=8 rats/group): Standard chow; standard chow + losartan; high‑fat diet; and high‑fat diet + losartan. At 10 weeks of age, treatment with losartan was discontinued. Rats were followed up until 26 weeks of age. Obesity, dyslipidemia, hyperglycemia, abnormal adipokine secretion, larger adipocytes and decreased expression of markers of adipocyte differentiation were present in high‑fat‑fed SHRs, and were attenuated in losartan‑treated rats. The increased expression and promoter hypomethylation of AT1R subtype a (AT1aR) in the adipose tissue of high‑fat‑fed SHRs were reversed by treatment with losartan. No difference was observed in the expression and promoter methylation of AT1R subtype b (AT1bR) among the four groups. Decreased expression and promoter hypermethylation of ATRAP were demonstrated in the adipose tissue of high‑fat‑fed SHRs. However, losartan made no difference to the expression and promoter methylation of ATRAP. Prehypertensive losartan therapy may relieve metabolic disorders in the later life of high‑fat‑fed SHRs. Differential epigenetic regulation of AT1aR and ATRAP expression through DNA methylation in adipose tissue may be involved in the long‑term beneficial effect.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

View References

1 

Galassi A, Reynolds K and He J: Metabolic syndrome and risk of cardiovascular disease: A meta-analysis. Am J Med. 119:812–819. 2006. View Article : Google Scholar

2 

Peng F, Lin J, Lin L and Tang H: Transient prehypertensive treatment in spontaneously hypertensive rats: A comparison of losartan and amlodipine regarding long-term blood pressure, cardiac and renal protection. Int J Mol Med. 30:1376–1386. 2012. View Article : Google Scholar

3 

Maury E and Brichard SM: Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 314:1–16. 2010. View Article : Google Scholar

4 

Jing F, Mogi M and Horiuchi M: Role of renin-angiotensin-aldosterone system in adipose tissue dysfunction. Mol Cell Endocrinol. 378:23–28. 2013. View Article : Google Scholar

5 

Lastra G and Sowers JR: Obesity and cardiovascular disease: Role of adipose tissue, inflammation, and the renin-angiotensin-aldosterone system. Horm Mol Biol Clin Investig. 15:49–57. 2013.

6 

Bogdarina I, Welham S, King PJ, Burns SP and Clark AJ: Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. Circ Res. 100:520–526. 2007. View Article : Google Scholar :

7 

Xiao D, Dasgupta C, Li Y, Huang X and Zhang L: Perinatal nicotine exposure increases angiotensin II receptor-mediated vascular contractility in adult offspring. PLoS One. 9:e1081612014. View Article : Google Scholar :

8 

Mao C, Liu R, Bo L, Chen N, Li S, Xia S, Chen J, Li D, Zhang L and Xu Z: High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system. J Endocrinol. 218:61–73. 2013. View Article : Google Scholar :

9 

Schübeler D: Function and information content of DNA methylation. Nature. 517:321–326. 2015. View Article : Google Scholar

10 

Jones PA: Functions of DNA methylation: Islands, start sites, gene bodies and beyond. Nat Rev Genet. 13:484–492. 2012. View Article : Google Scholar

11 

Deaton AM and Bird A: CpG islands and the regulation of transcription. Genes Dev. 25:1010–1022. 2011. View Article : Google Scholar :

12 

Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 355:253–259. 2000. View Article : Google Scholar

13 

Maeda A, Tamura K, Wakui H, Ohsawa M, Azushima K, Uneda K, Kobayashi R, Tsurumi-Ikeya Y, Kanaoka T, Dejima T, et al: Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders. Int J Med Sci. 11:646–651. 2014. View Article : Google Scholar :

14 

Fernandez-Twinn DS and Ozanne SE: Early life nutrition and metabolic programming. Ann N Y Acad Sci. 1212:78–96. 2010. View Article : Google Scholar

15 

Lindl T, Gross U, Ruhdel I, von Aulock S and Völkel M: Guidance on determining indispensability and balancing potential benefits of animal experiments with costs to the animals with specific consideration of EU directive 2010/63/EU. Altex. 29:219–228. 2012. View Article : Google Scholar

16 

Ray MA, Johnston NA, Verhulst S, Trammell RA and Toth LA: Identification of markers for imminent death in mice used in longevity and aging research. J Am Assoc Lab Anim Sci. 49:282–288. 2010.

17 

Widdop RE and Li XC: A simple versatile method for measuring tail cuff systolic blood pressure in conscious rats. Clin Sci (Lond). 93:191–194. 1997. View Article : Google Scholar

18 

Xie LD, Chen DG, Zhang S, Wang HJ and Chen HJ: Sympatholytic effect of captopril in regression of cardiovascular remodeling in spontaneously hypertensive rats. Zhongguo Yao Li Xue Bao. 15:123–128. 1994.

19 

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

20 

Xie LD, Lin PS, Xie H and Xu CS: Effects of atorvastatin and losartan on monocrotaline-induced pulmonary artery remodeling in rats. Clin Exp Hypertens. 32:547–554. 2011. View Article : Google Scholar

21 

Chen HF, Xie LD and Xu CS: The signal transduction pathways of heat shock protein 27 phosphorylation in vascular smooth muscle cells. Mol Cell Biochem. 333:49–56. 2010. View Article : Google Scholar

22 

Wang TJ, Lin X, Lian GL, Zhong HB and Xie LD: The effect of early losartan treatment on methylation of angiotensin II type 1 receptor subtype b and angiotensin II type 1 receptor associated protein genes in the myocardium of spontaneously hypertensive rats. Chin J Hypertens. 24:141–146. 2016. View Article : Google Scholar

23 

Lee AM, Gurka MJ and DeBoer MD: Trends in metabolic syndrome severity and lifestyle factors among adolescents. Pediatrics. 137:e201531772016. View Article : Google Scholar :

24 

Knight SF, Quigley JE, Yuan J, Roy SS, Elmarakby A and Imig JD: Endothelial dysfunction and the development of renal injury in spontaneously hypertensive rats fed a high-fat diet. Hypertension. 51:352–359. 2008. View Article : Google Scholar

25 

Cao J, Inoue K, Sodhi K, Puri N, Peterson SJ, Rezzani R and Abraham NG: High-fat diet exacerbates renal dysfunction in SHR: Reversal by induction of HO-1-adiponectin axis. Obesity (Silver Spring). 20:945–953. 2012. View Article : Google Scholar

26 

Tontonoz P and Spiegelman BM: Fat and beyond: The diverse biology of PPARgamma. Annu Rev Biochem. 77:289–312. 2008. View Article : Google Scholar

27 

Singh KD and Karnik SS: Angiotensin receptors: Structure, function, signaling and clinical applications. J Cell Signal. 1:pii: 111. 2016.

28 

Tamura K, Wakui H, Maeda A, Dejima T, Ohsawa M, Azushima K, Kanaoka T, Haku S, Uneda K, Masuda S, et al: The physiology and pathophysiology of a novel angiotensin receptor-binding protein ATRAP/Agtrap. Curr Pharm Des. 19:3043–3048. 2013. View Article : Google Scholar

29 

Shigenaga A, Tamura K, Wakui H, Masuda S, Azuma K, Tsurumi-Ikeya Y, Ozawa M, Mogi M, Matsuda M, Uchino K, et al: Effect of olmesartan on tissue expression balance between angiotensin II receptor and its inhibitory binding molecule. Hypertension. 52:672–678. 2008. View Article : Google Scholar

30 

Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Naslund E, Britton T, et al: Dynamics of fat cell turnover in humans. Nature. 453:783–787. 2008. View Article : Google Scholar

31 

Li Y, Xiao D, Yang S and Zhang L: Promoter methylation represses AT2R gene and increases brain hypoxic-ischemic injury in neonatal rats. Neurobiol Dis. 60:32–38. 2013. View Article : Google Scholar

32 

McKinsey TA: Therapeutic potential for HDAC inhibitors in the heart. Annu Rev Pharmacol Toxicol. 52:303–319. 2012. View Article : Google Scholar

33 

Xiao D, Dasgupta C, Chen M, Zhang K, Buchholz J, Xu Z and Zhang L: Inhibition of DNA methylation reverses norepinephrine-induced cardiac hypertrophy in rats. Cardiovasc Res. 101:373–382. 2014. View Article : Google Scholar

34 

Cho HM, Lee HA, Kim HY, Han HS and Kim IK: Expression of Na+−K+ −2Cl− cotransporter 1 is epigenetically regulated during postnatal development of hypertension. Am J Hypertens. 24:1286–1293. 2011. View Article : Google Scholar

35 

Wu Z, Siuda D, Xia N, Reifenberg G, Daiber A, Münzel T, Förstermann U and Li H: Maternal treatment of spontaneously hypertensive rats with pentaerythritol tetranitrate reduces blood pressure in female offspring. Hypertension. 65:232–237. 2015. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang T, Lian G, Cai X, Lin Z and Xie L: Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats. Mol Med Rep 17: 1753-1761, 2018.
APA
Wang, T., Lian, G., Cai, X., Lin, Z., & Xie, L. (2018). Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats. Molecular Medicine Reports, 17, 1753-1761. https://doi.org/10.3892/mmr.2017.8081
MLA
Wang, T., Lian, G., Cai, X., Lin, Z., Xie, L."Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats". Molecular Medicine Reports 17.1 (2018): 1753-1761.
Chicago
Wang, T., Lian, G., Cai, X., Lin, Z., Xie, L."Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats". Molecular Medicine Reports 17, no. 1 (2018): 1753-1761. https://doi.org/10.3892/mmr.2017.8081
Copy and paste a formatted citation
x
Spandidos Publications style
Wang T, Lian G, Cai X, Lin Z and Xie L: Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats. Mol Med Rep 17: 1753-1761, 2018.
APA
Wang, T., Lian, G., Cai, X., Lin, Z., & Xie, L. (2018). Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats. Molecular Medicine Reports, 17, 1753-1761. https://doi.org/10.3892/mmr.2017.8081
MLA
Wang, T., Lian, G., Cai, X., Lin, Z., Xie, L."Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats". Molecular Medicine Reports 17.1 (2018): 1753-1761.
Chicago
Wang, T., Lian, G., Cai, X., Lin, Z., Xie, L."Effect of prehypertensive losartan therapy on AT1R and ATRAP methylation of adipose tissue in the later life of high‑fat‑fed spontaneously hypertensive rats". Molecular Medicine Reports 17, no. 1 (2018): 1753-1761. https://doi.org/10.3892/mmr.2017.8081
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