Skip to main content
SpringerLink
Log in

Connexin43 siRNA promotes HUVEC proliferation and inhibits apoptosis induced by ox-LDL: an involvement of ERK signaling pathway

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Oxidized low-density lipoprotein (ox-LDL), one of the most important risk factors of atherosclerosis, is a highly antigenic, potent chemoattractant that facilitates the development of atherosclerosis. Gap junctions also play an important in the development of atherosclerosis. In this study, we investigated the effects of ox-LDL on connexin43 and the mechanisms of connexin43 siRNA-inhibited apoptosis induced by ox-LDL in human umbilical vein endothelial cell (HUVEC), to clarify the role of connexin43 in atherosclerosis. Our results showed that ox-LDL significantly inhibited the growth and promoted apoptosis of HUVEC in a dose-dependent manner. Also, ox-LDL upregulated the expression of connexin43. Furthermore, knockdown connexin43 by siRNA promoted proliferation and inhibited apoptosis in ox-LDL-stimulated HUVEC. Moreover, the level of phosphor-ERK1/2 and connexin43 was remarkably attenuated by a ERK pathway inhibitor (PD98059). These results suggest that connexin43 siRNA promotes HUVEC proliferation and inhibits apoptosis induced by ox-LDL, and ERK signaling pathway appears to be involved in these processes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

PTCA:

Percutaneous transluminal coronary angioplasty

Ox-LDL:

Oxidized low-density lipoprotein

HUVEC:

Human umbilical vein endothelial cell

References

  1. Libby P, DiCarli M, Weissleder R (2010) The vascular biology of atherosclerosis and imaging targets. J Nucl Med 51:33S–37S

    Article  PubMed  Google Scholar 

  2. Chen LJ, Lim SH, Yeh YT et al (2012) Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci 19:79–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Bernat R, Szavits-Nossan J, Trbovic A et al (2012) Relationship of genetic markers for atherosclerosis and long-term outcome after percutaneous coronary intervention with stenting. Coll Antropol 36:1385–1390

    CAS  PubMed  Google Scholar 

  4. Kozak O, Tariq N, Suri MFK et al (2011) High risk of recurrent ischemic events among patients with deferred intracranial angioplasty and stent placement for symptomatic intracranial atherosclerosis. Neurosurgery 69:334–343

    Article  PubMed  Google Scholar 

  5. Adiguzel E, Ahmad PJ, Franco C et al (2009) Collagens in the progression and complications of atherosclerosis. Vas Med 14:73–89

    Article  Google Scholar 

  6. Corbi G, Bianco A, Turchiarelli V et al (2013) Potential mechanisms linking atherosclerosis and increased cardiovascular risk in COPD: focus on sirtuins. Int J Mol Sci 14:12696–12713

    Article  PubMed Central  PubMed  Google Scholar 

  7. Roy A, Kolattukudy PE (2012) Monocyte chemotactic protein-induced protein (MCPIP) promotes inflammatory angiogenesis via sequential induction of oxidative stress, endoplasmic reticulum stress and autophagy. Cell Signal 24:2123–2131

    Article  CAS  PubMed  Google Scholar 

  8. Vanhoutte PM (2009) Endothelial dysfunction: the first step toward coronary arteriosclerosis. Circ J 73:595–601

    Article  CAS  PubMed  Google Scholar 

  9. Grover-Páez F, Zavalza-Gómez AB (2009) Endothelial dysfunction and cardiovascular risk factors. Diabetes Res Clin 84:1–10

    Article  Google Scholar 

  10. Yang H, Mohamed ASS, Zhou SH (2012) Oxidized low density lipoprotein, stem cells, and atherosclerosis. Lipids Health Dis 11:85–92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Morel S, Burnier L, Kwak BR (2009) Connexins participate in the initiation and progression of atherosclerosis. Semin Immunopathol 31:49–61

    Article  CAS  PubMed  Google Scholar 

  12. Ruan LM, Cai W, Chen JZ et al (2010) Effects of Losartan on expression of connexins at the early stage of atherosclerosis in rabbits. Int J Med Sci 7:82–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Cai W, Ruan LM, Wang YN et al (2006) Effects of angiotensin II on connexin 43 of VSMCs in arteriosclerosis. J Zhejiang Univ Sci 7:648–653

    Article  CAS  Google Scholar 

  14. Kwak BR, Mulhaupt F, Veillard N et al (2002) Altered pattern of vascular connexin expression in atherosclerotic plaques. Arterioscl Throm Vas 22:225–230

    Article  CAS  Google Scholar 

  15. Chadjichristos CE, Scheckenbach KEL, van Veen TAB et al (2010) Endothelial-specific deletion of connexin40 promotes atherosclerosis by increasing CD73-dependent leukocyte adhesion. Circulation 121:123–131

    Article  CAS  PubMed  Google Scholar 

  16. Chen LJ, Lim SH, Yeh YT et al (2012) Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci 9:79–90

    Article  Google Scholar 

  17. Zhang Y, Li L, You J et al (2013) Effect of 7-Difluoromethyl-5, 4′-dimethoxygenistein on aorta atherosclerosis in hyperlipidemia ApoE−/− mice induced by a cholesterol-rich diet. Drug Des Dev Ther 7:233–242

    Article  CAS  Google Scholar 

  18. Zhang X, Li H, Jin H et al (2000) Effects of homocysteine on endothelial nitric oxide production. Am J Physiol-Renal 279:F671–F678

    CAS  Google Scholar 

  19. Gimbrone MA, Topper JN, Nagel T et al (2000) Endothelial dysfunction, hemodynamic forces, and atherogenesisa. Ann N Y Acad Sci 902:230–240

    Article  CAS  PubMed  Google Scholar 

  20. Riwanto M, Rohrer L, Roschitzki B et al (2013) Altered activation of endothelial anti-and proapoptotic pathways by high-density lipoprotein from patients with coronary artery diseaseclinical perspective role of high-density lipoprotein-proteome remodeling. Circulation 127:891–904

    Article  CAS  PubMed  Google Scholar 

  21. Krysko D, Leybaert L, Vandenabeele P et al (2005) Gap junctions and the propagation of cell survival and cell death signals. Apoptosis 10:459–469

    Article  CAS  PubMed  Google Scholar 

  22. Wei CJ, Xu X, Lo CW (2004) Connexins and cell signaling in development and disease. Annu Rev Cell Dev Biol 20:811–838

    Article  CAS  PubMed  Google Scholar 

  23. Rodríguez-Sinovas A, Cabestrero A, López D et al (2007) The modulatory effects of connexin 43 on cell death/survival beyond cell coupling. Prog Biophys Mol Bio 94:219–232

    Article  Google Scholar 

  24. Zhang S, Hong M, Gao Y (2012) Effect of oxidized LDL on the expression of connexins in cultured human umbilical-vein endothelial cells. Cell Biol Int 36:497–502

    Article  PubMed  Google Scholar 

  25. Plotkin L, Bellido T (2001) Bisphosphonate-induced, hemichannel-mediated, anti-apoptosis through the Src/ERK pathway: a gap junction-independent action of connexin43. Cell Commun Adhes 8:377–382

    Article  CAS  PubMed  Google Scholar 

  26. Dimmeler S, Zeiher AM (2000) Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res 87:434–439

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Cardiology, Third Affiliated Hospital, Xinxiang Medical University, Xinxiang City, 453003, Henan, China

    Guotian Yin, Xiuli Yang, Bo Li & Meng Yang

  2. Department of Cardiology, Second Affiliated Hospital, Xinxiang Medical University, Xinxiang City, 453003, Henan, China

    Mingfen Ren

Authors
  1. Guotian Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiuli Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Meng Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingfen Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mingfen Ren.

Additional information

Guotian Yin and Xiuli Yang contributed equally to this work and are considered co-first authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yin, G., Yang, X., Li, B. et al. Connexin43 siRNA promotes HUVEC proliferation and inhibits apoptosis induced by ox-LDL: an involvement of ERK signaling pathway. Mol Cell Biochem 394, 101–107 (2014). https://doi.org/10.1007/s11010-014-2085-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-014-2085-4

Keywords

Search

Navigation