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Article Open Access

GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription

  • Authors:
    • Hongfei Xu
    • Zhen Wang
    • Zewei Sun
    • Yiming Ni
    • Liangrong Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Cardiothoracic Surgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China, Department of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1485-1492
    |
    Published online on: November 14, 2017
       https://doi.org/10.3892/mmr.2017.8062
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Abstract

Endothelial dysfunction is one of the most common complications associated with diabetes and may lead to atherosclerosis. Conflicting reports indicate that NADPH oxidase 4 (NOX4) induces hydrogen peroxide production and cytotoxicity, but also has a protective effect on endothelial dysfunction. The present study aimed to identify the transcription factor responsible for NOX4 expression using a transcription factor activation profiling plate array and chromatin immunoprecipitation. Data from these analyses indicated that GATA‑binding protein 4 (GATA4) was able to mediate NOX4 transcription and is downregulated in human umbilical vein endothelial cells (HUVECs) that were exposed to hyperglycemic conditions as well as in the endothelial cells of a mouse diabetes model. Overexpression of GATA4 was demonstrated to lead to increased expression of NOX4 mRNA and protein. Furthermore, GATA4 overexpression resulted in increased nitric oxide (NO) production through the upregulation of endothelial NO synthase phosphorylation. Treatment with simvastatin, a drug known to preserve endothelial function through an unknown mechanism, improved endothelial cell function by upregulating GATA4 expression in HUVECs exposed to hyperglycemia. Results from these experiments demonstrated that GATA4 may inhibit diabetes‑induced endothelial dysfunction by acting as a transcription factor for NOX4 expression and increasing NO production. Thus, the present study revealed a novel molecular mechanism underlying endothelial dysfunction in diabetes and identified GATA4 as a potential therapeutic target.
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1 

Mellbin LG, Anselmino M and Rydén L: Diabetes, prediabetes and cardiovascular risk. Eur J Cardiovasc Prev Rehabil. 17 Suppl 1:S9–S14. 2010. View Article : Google Scholar

2 

Riddle MC: Glycemic control and cardiovascular mortality. Curr Opin Endocrinol Diabetes Obes. 18:104–109. 2011. View Article : Google Scholar

3 

Bentzon JF, Otsuka F, Virmani R and Falk E: Mechanisms of plaque formation and rupture. Circ Res. 114:1852–1866. 2014. View Article : Google Scholar

4 

Sun Z: Atherosclerosis and atheroma plaque rupture: Normal anatomy of vasa vasorum and their role associated with atherosclerosis. ScientificWorldJournal. 2014:2850582014.

5 

Polovina MM and Potpara TS: Endothelial dysfunction in metabolic and vascular disorders. Postgrad Med. 126:38–53. 2014. View Article : Google Scholar

6 

Bondarenko PG and Sil'Chenko TS: Status of the immune system in peptic ulcer patients before and after vagotomy. Klin Khir. 27–29. 1983.(In Russian).

7 

Langbein H, Brunssen C, Hofmann A, Cimalla P, Brux M, Bornstein SR, Deussen A, Koch E and Morawietz H: NADPH oxidase 4 protects against development of endothelial dysfunction and atherosclerosis in LDL receptor deficient mice. Eur Heart J. 37:1753–1761. 2016. View Article : Google Scholar

8 

Kleinschnitz C, Grund H, Wingler K, Armitage ME, Jones E, Mittal M, Barit D, Schwarz T, Geis C, Kraft P, et al: Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol. 8:pii: e1000479. 2010. View Article : Google Scholar :

9 

Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD and Sadoshima J: NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA. 107:15565–15570. 2010. View Article : Google Scholar :

10 

Ray R, Murdoch CE, Wang M, Santos CX, Zhang M, Alom-Ruiz S, Anilkumar N, Ouattara A, Cave AC, Walker SJ, et al: Endothelial Nox4 NADPH oxidase enhances vasodilatation and reduces blood pressure in vivo. Arterioscler Thromb Vasc Biol. 31:1368–1376. 2011. View Article : Google Scholar

11 

Manea SA, Todirita A, Raicu M and Manea A: C/EBP transcription factors regulate NADPH oxidase in human aortic smooth muscle cells. J Cell Mol Med. 18:1467–1477. 2014. View Article : Google Scholar :

12 

Manea A, Tanase LI, Raicu M and Simionescu M: Jak/STAT signaling pathway regulates nox1 and nox4-based NADPH oxidase in human aortic smooth muscle cells. Arterioscler Thromb Vasc Biol. 30:105–112. 2010. View Article : Google Scholar

13 

Sun Z, Han J, Zhao W, Zhang Y, Wang S, Ye L, Liu T and Zheng L: TRPV1 activation exacerbates hypoxia/reoxygenation-induced apoptosis in H9C2 cells via calcium overload and mitochondrial dysfunction. Int J Mol Sci. 15:18362–18380. 2014. View Article : Google Scholar :

14 

Zhao C, Guo H, Li J, Myint T, Pittman W, Yang L, Zhong W, Schwartz RJ, Schwarz JJ, Singer HA, et al: Numb family proteins are essential for cardiac morphogenesis and progenitor differentiation. Development. 141:281–295. 2014. View Article : Google Scholar :

15 

Zhong X, Xiu LL, Wei GH, Liu YY, Su L, Cao XP, Li YB and Xiao HP: Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation. Acta Pharmacol Sin. 32:591–600. 2011. View Article : Google Scholar :

16 

Hou HH, Liao YJ, Hsiao SH, Shyue SK and Lee TS: Role of phosphatase activity of soluble epoxide hydrolase in regulating simvastatin-activated endothelial nitric oxide synthase. Sci Rep. 5:135242015. View Article : Google Scholar :

17 

Murray TV, Smyrnias I, Shah AM and Brewer AC: NADPH oxidase 4 regulates cardiomyocyte differentiation via redox activation of c-Jun protein and the cis-regulation of GATA-4 gene transcription. J Biol Chem. 288:15745–15759. 2013. View Article : Google Scholar :

18 

Tremblay JJ, Hamel F and Viger RS: Protein kinase A-dependent cooperation between GATA and CCAAT/enhancer-binding protein transcription factors regulates steroidogenic acute regulatory protein promoter activity. Endocrinology. 143:3935–3945. 2002. View Article : Google Scholar

19 

LaVoie HA, Singh D and Hui YY: Concerted regulation of the porcine steroidogenic acute regulatory protein gene promoter activity by follicle-stimulating hormone and insulin-like growth factor I in granulosa cells involves GATA-4 and CCAAT/enhancer binding protein beta. Endocrinology. 145:3122–3134. 2004. View Article : Google Scholar

20 

Broderick TL, Parrott CR, Wang D, Jankowski M and Gutkowska J: Expression of cardiac GATA4 and downstream genes after exercise training in the db/db mouse. Pathophysiology. 19:193–203. 2012. View Article : Google Scholar

21 

Broderick TL, Jankowski M, Wang D, Danalache BA, Parrott CR and Gutkowska J: Downregulation in GATA4 and downstream structural and contractile genes in the db/db mouse heart. ISRN Endocrinol. 2012:7368602012. View Article : Google Scholar :

22 

Shaw-Smith C, De Franco E, Allen Lango H, Batlle M, Flanagan SE, Borowiec M, Taplin CE, van Alfen-van der Velden J, Cruz-Rojo J, de Nanclares Perez G, et al: GATA4 mutations are a cause of neonatal and childhood-onset diabetes. Diabetes. 63:2888–2894. 2014. View Article : Google Scholar

23 

Muiya NP, Wakil SM, Tahir AI, Hagos S, Najai M, Gueco D, Al-Tassan N, Andres E, Mazher N, Meyer BF and Dzimiri N: A study of the role of GATA4 polymorphism in cardiovascular metabolic disorders. Hum Genomics. 7:252013. View Article : Google Scholar :

24 

Vaskivuo TE, Anttonen M, Herva R, Billig H, Dorland M, te Velde ER, Stenbäck F, Heikinheimo M and Tapanainen JS: Survival of human ovarian follicles from fetal to adult life: Apoptosis, apoptosis-related proteins, and transcription factor GATA-4. J Clin Endocrinol Metab. 86:3421–3429. 2001. View Article : Google Scholar

25 

Li HX, Zhou YF, Zhao X, Jiang B and Yang XJ: GATA-4 protects against hypoxia-induced cardiomyocyte injury: Effects on mitochondrial membrane potential. Can J Physiol Pharmacol. 92:669–678. 2014. View Article : Google Scholar

26 

Bielli A, Scioli MG, Mazzaglia D, Doldo E and Orlandi A: Antioxidants and vascular health. Life Sci. 143:209–216. 2015. View Article : Google Scholar

27 

Aries A, Paradis P, Lefebvre C, Schwartz RJ and Nemer M: Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity. Proc Natl Acad Sci USA. 101:6975–6980. 2004. View Article : Google Scholar :

28 

Kobayashi S, Lackey T, Huang Y, Bisping E, Pu WT, Boxer LM and Liang Q: Transcription factor gata4 regulates cardiac BCL2 gene expression in vitro and in vivo. FASEB J. 20:800–802. 2006.

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Copy and paste a formatted citation
Spandidos Publications style
Xu H, Wang Z, Sun Z, Ni Y and Zheng L: GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription. Mol Med Rep 17: 1485-1492, 2018.
APA
Xu, H., Wang, Z., Sun, Z., Ni, Y., & Zheng, L. (2018). GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription. Molecular Medicine Reports, 17, 1485-1492. https://doi.org/10.3892/mmr.2017.8062
MLA
Xu, H., Wang, Z., Sun, Z., Ni, Y., Zheng, L."GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription". Molecular Medicine Reports 17.1 (2018): 1485-1492.
Chicago
Xu, H., Wang, Z., Sun, Z., Ni, Y., Zheng, L."GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription". Molecular Medicine Reports 17, no. 1 (2018): 1485-1492. https://doi.org/10.3892/mmr.2017.8062
Copy and paste a formatted citation
x
Spandidos Publications style
Xu H, Wang Z, Sun Z, Ni Y and Zheng L: GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription. Mol Med Rep 17: 1485-1492, 2018.
APA
Xu, H., Wang, Z., Sun, Z., Ni, Y., & Zheng, L. (2018). GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription. Molecular Medicine Reports, 17, 1485-1492. https://doi.org/10.3892/mmr.2017.8062
MLA
Xu, H., Wang, Z., Sun, Z., Ni, Y., Zheng, L."GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription". Molecular Medicine Reports 17.1 (2018): 1485-1492.
Chicago
Xu, H., Wang, Z., Sun, Z., Ni, Y., Zheng, L."GATA4 protects against hyperglycemia‑induced endothelial dysfunction by regulating NOX4 transcription". Molecular Medicine Reports 17, no. 1 (2018): 1485-1492. https://doi.org/10.3892/mmr.2017.8062
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