Skip to main content
SpringerLink
Log in

RETRACTED ARTICLE: The role of cystatin C in vascular remodeling of balloon-injured abdominal aorta of rabbits

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

This article was retracted on 18 August 2015

Abstract

This study aimed to evaluate the role of cystatin C (CysC) in the vascular remodeling of balloon-injured abdominal aorta of rabbits. Forty-eight New Zealand white rabbits were randomly divided into three groups: the balloon-injured injury group (n = 16), the CysC monoclonal antibody group (n = 16), and the sham-operative group (n = 16). Serum CysC levels were detected by enzyme linked immunosorbent assay. Changes in adventitial area, adventitial thickness, lumen area (LA), neointimal area (IA), internal elastic lamina area (IELA), external elastic lamina area (EELA), vascular remodeling index (VRI) and residual stenosis (RS) were measured by the Leica image analysis system. Immunohistochemical analysis of α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) were performed. Serum CysC levels of rabbits in the balloon-injured injury group were significantly higher than those in the CysC monoclonal antibody group and the sham-operative group (both P < 0.05). At 6 weeks after balloon injury, the adventitial area and thickness, LA, IA, IELA and EELA in the balloon-injured injury group were also higher than those in the CysC monoclonal antibody and sham-operative groups (all P < 0.05). In addition, the balloon-injured injury group showed higher VRI and RS than those of the CysC monoclonal antibody group (both P < 0.05). The positive expression of α-SMA in the vascular adventitia and media in the balloon-injured group were higher than that of the CysC monoclonal antibody and sham-operative groups. The balloon-injured group also showed a stronger expression of α-SMA in the neointima than that of the CysC monoclonal antibody group. There was a strong positive expression of PCNA in the vascular adventitia and neointima in the balloon-injured and CysC monoclonal antibody groups. However, the number of PCNA-positive cells in the balloon-injured group was higher than that of the CysC monoclonal antibody group (25.45 ± 4.21 vs. 6.75 ± 1.11, P = 0.003). Our findings provide empirical evidence that serum CysC levels may play an important role in the vascular remodeling of balloon-injured abdominal aorta of rabbits.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Liu J, Sukhova GK, Sun JS, Xu WH, Libby P, Shi GP (2004) Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol 24:1359–1366. doi:10.1161/01.ATV.0000134530.27208.41

    Article  CAS  PubMed  Google Scholar 

  2. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S (2007) Cathepsin cysteine proteases in cardiovascular disease. FASEB J 21:3029–3041. doi:10.1096/fj.06-7924com

    Article  CAS  PubMed  Google Scholar 

  3. Niccoli G, Conte M, Della Bona R, Altamura L, Siviglia M, Dato I, Ferrante G, Leone AM et al (2008) Cystatin c is associated with an increased coronary atherosclerotic burden and a stable plaque phenotype in patients with ischemic heart disease and normal glomerular filtration rate. Atherosclerosis 198:373–380. doi:10.1016/j.atherosclerosis.2007.09.022

    Article  CAS  PubMed  Google Scholar 

  4. Lafarge JC, Naour N, Clement K, Guerre-Millo M (2010) Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie 92:1580–1586. doi:10.1016/j.biochi.2010.04.011

    Article  CAS  PubMed  Google Scholar 

  5. Shlipak MG, Sarnak MJ, Katz R, Fried LF, Seliger SL, Newman AB, Siscovick DS, Stehman-Breen C (2005) Cystatin c and the risk of death and cardiovascular events among elderly persons. N Engl J Med 352:2049–2060. doi:10.1056/NEJMoa043161

    Article  CAS  PubMed  Google Scholar 

  6. Taglieri N, Koenig W, Kaski JC (2009) Cystatin C and cardiovascular risk. Clin Chem 55:1932–1943. doi:10.1373/clinchem

    Article  CAS  PubMed  Google Scholar 

  7. Yamamoto T, Shimano M, Inden Y, Miyata S, Inoue Y, Yoshida N, Tsuji Y, Hirai M et al (2013) Cystatin C as a predictor of mortality and cardiovascular morbidity after cardiac resynchronization therapy. Circ J 77:2751–2756. doi:10.1253/circj.CJ-13-0179

    Article  PubMed  Google Scholar 

  8. Angelidis C, Deftereos S, Giannopoulos G, Anatoliotakis N, Bouras G, Hatzis G, Panagopoulou V, Pyrgakis V et al (2013) Cystatin C: an emerging biomarker in cardiovascular disease. Curr Top Med Chem 13:164–179

    Article  CAS  PubMed  Google Scholar 

  9. Bengtsson E, To F, Hakansson K, Grubb A, Branen L, Nilsson J, Jovinge S (2005) Lack of the cysteine protease inhibitor cystatin C promotes atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 25:2151–2156. doi:10.1161/01.ATV.0000179600.34086.7d

    Article  CAS  PubMed  Google Scholar 

  10. Hoke M, Amighi J, Mlekusch W, Schlager O, Exner M, Sabeti S, Dick P, Koppensteiner R et al (2010) Cystatin C and the risk for cardiovascular events in patients with asymptomatic carotid atherosclerosis. Stroke 41:674–679. doi:10.1161/STROKEAHA.109.573162

    Article  CAS  PubMed  Google Scholar 

  11. Shlipak MG, Katz R, Sarnak MJ, Fried LF, Newman AB, Stehman-Breen C, Seliger SL, Kestenbaum B et al (2006) Cystatin c and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann Intern Med 145:237–246

    Article  CAS  PubMed  Google Scholar 

  12. Song JW, Cheng YB, Yin JG, Geng XN, Jia X, Liu XH, Yang Y (2004) Study on the dynamic change of endothelin in the development of stenosis of aorta after balloon injury in rabbits. J Interv Radiol 13:446–449. doi:10.3969/j.issn.1008-794X.2004.05.022

    Google Scholar 

  13. Wu XJ, Lu QH (2013) Expression and significance of α-SMA and PCNA in the vascular adventitia of balloon-injured rat aorta. Exp Ther Med 5:1671–1676. doi:10.3892/etm.2013.1059

    PubMed Central  PubMed  Google Scholar 

  14. Kwon ST, Rectenwald JE, Baek S (2011) Intrasac pressure changes and vascular remodeling after endovascular repair of abdominal aortic aneurysms: review and biomechanical model simulation. J Biomech Eng 133:011011. doi:10.1115/1.4003134

    Article  CAS  PubMed  Google Scholar 

  15. Humphrey JD (2008) Mechanisms of arterial remodeling in hypertension: coupled roles of wall shear and intramural stress. Hypertension 52:195–200. doi:10.1161/HYPERTENSIONAHA.107.103440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y (2008) Exercise, vascular wall and cardiovascular diseases: an update (part 1). Sports Med 38:1009–1024. doi:10.2165/00007256-200838120-00005

    Article  PubMed  Google Scholar 

  17. Remuzzi A, Ene-Iordache B (2013) Novel paradigms for dialysis vascular access: upstream hemodynamics and vascular remodeling in dialysis access stenosis. Clin J Am Soc Nephrol 8:2186–2193. doi:10.2215/CJN.03450413

    Article  PubMed Central  PubMed  Google Scholar 

  18. Saito T, Iguchi A, Tabayashi K (2009) Irradiation inhibits vascular anastomotic stenosis in a canine model. Gen Thorac Cardiovasc Surg 57:406–412. doi:10.1007/s11748-009-0413-5

    Article  PubMed  Google Scholar 

  19. Nugent HM, Ng YS, White D, Groothius A, Kanner G, Edelman ER (2012) Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular injury in a porcine model. J Vasc Surg 56:1078–1088. doi:10.1016/j.jvs.2012.03.002

    Article  PubMed Central  PubMed  Google Scholar 

  20. Gregory EK, Vavra AK, Moreira ES, Havelka GE, Jiang Q, Lee VR, Van Lith R, Ameer GA et al (2011) Antioxidants modulate the antiproliferative effects of nitric oxide on vascular smooth muscle cells and adventitial fibroblasts by regulating oxidative stress. Am J Surg 202:536–540. doi:10.1016/j.amjsurg.2011.06.018

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Coen M, Gabbiani G, Bochaton-Piallat ML (2011) Myofibroblast-mediated adventitial remodeling: an underestimated player in arterial pathology. Arterioscler Thromb Vasc Biol 31:2391–2396. doi:10.1161/ATVBAHA.111.231548

    Article  CAS  PubMed  Google Scholar 

  22. Stenmark KR, Yeager ME, El Kasmi KC, Nozik-Grayck E, Gerasimovskaya EV, Li M, Riddle SR, Frid MG (2013) The adventitia: essential regulator of vascular wall structure and function. Ann Rev Physiol 75:23–47. doi:10.1146/annurev-physiol-030212-183802

    Article  CAS  Google Scholar 

  23. Forte A, Della Corte A, De Feo M, Cerasuolo F, Cipollaro M (2010) Role of myofibroblasts in vascular remodelling: focus on restenosis and aneurysm. Cardiovasc Res 88:395–405. doi:10.1093/cvr/cvq224

    Article  CAS  PubMed  Google Scholar 

  24. Maiellaro K, Taylor WR (2007) The role of the adventitia in vascular inflammation. Cardiovasc Res 75:640–648. doi:10.1016/j.cardiores.2007.06.023

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Otranto M, Sarrazy V, Bonte F, Hinz B, Gabbiani G, Desmouliere A (2012) The role of the myofibroblast in tumor stroma remodeling. Cell Adh Migr 6:203–219. doi:10.4161/cam.20377

    Article  PubMed Central  PubMed  Google Scholar 

  26. Jin X, Fu GX, Li XD, Zhu DL, Gao PJ (2011) Expression and function of osteopontin in vascular adventitial fibroblasts and pathological vascular remodeling. PLoS ONE 6:e23558. doi:10.1371/journal.pone.0023558

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Lee T, Chauhan V, Krishnamoorthy M, Wang Y, Arend L, Mistry MJ, El-Khatib M, Banerjee R et al (2011) Severe venous neointimal hyperplasia prior to dialysis access surgery. Nephrol Dial Transplant 26:2264–2270. doi:10.1093/ndt/gfq733

    Article  PubMed Central  PubMed  Google Scholar 

  28. Shi GP, Sukhova GK, Grubb A, Ducharme A, Rhode LH, Lee RT, Ridker PM, Libby P et al (1999) Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J Clin Investigat 104:1191–1197. doi:10.1172/JCI7709

    Article  CAS  Google Scholar 

  29. Smetana K (2002) Structural features of nucleoli in blood, leukemic, lymphoma and myeloma cells. Eur J Histochem 46:125–132

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge the helpful comments on this paper received from our reviewers.

Competing interests

We declare that we have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Cardiovascular Medicine, Second Hospital of Shandong University, Beiyuan Street No. 247, Jinan, 250033, People’s Republic of China

    Xiang-Jun Wu, Zhao-Qiang Dong & Qing-Hua Lu

  2. Department of Cardiovascular Medicine, Binzhou City People’s Hospital of Shandong Province, Binzhou, 256600, People’s Republic of China

    Xiang-Jun Wu

Authors
  1. Xiang-Jun Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zhao-Qiang Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing-Hua Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-Hua Lu.

Additional information

The Publisher and Editor retract this article in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation we have strong reason to believe that the peer review process was compromised.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, XJ., Dong, ZQ. & Lu, QH. RETRACTED ARTICLE: The role of cystatin C in vascular remodeling of balloon-injured abdominal aorta of rabbits. Mol Biol Rep 41, 6225–6231 (2014). https://doi.org/10.1007/s11033-014-3502-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-014-3502-1

Keywords

Search

Navigation