Skip to main content
SpringerLink
Log in

Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization

  • Translational Biomedical Research
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

We determined the effect of atorvastatin on myocardial apoptosis and caspase-8 activation following coronary microembolization (CME) in a rat model. For this, 50 rats were randomly and equally divided into CME; sham-operated (control); atorvastatin lavage; gastric lavage control; and caspase-8 inhibitor (CHO) groups. In CME animals, a microembolization ball was injected through the left ventricle. Sham animals were injected with normal saline (NS). Atorvastatin group received atorvastatin gastric lavage once-a-day, 1 week before surgery. Gastric lavage controls had similar lavage with NS. CHO group was i.p-injected (CHO: 10 mg/kg) 30 min before surgery. Cardiac indices in each group were determined by echocardiography 6-h postoperatively. TUNEL assay and western blot were used for myocardial apoptosis and expression of caspases-3/-8, respectively. Echocardiography data show that left ventricular ejection fraction (LVEF) in CME group was significantly decreased (P < 0.05) compared with sham controls. Besides, left ventricular fractional shortening (FS) and cardiac output (CO) were also decreased with an increase in left ventricular end-diastolic dimension (LVEDd). Atorvastatin and CHO animals had significantly improved (P < 0.05) cardiac function compared with CME group. Myocardial apoptosis and activation levels of caspases-3/-8 were significantly increased (P < 0.05) compared with sham; myocardial apoptosis and activation levels of caspases-3/-8 were significantly decreased (P < 0.05) in atorvastatin and CHO groups compared with CME group. In conclusion, atorvastatin pretreatment suppressed post-CME myocardial apoptosis and improved cardiac function through the blockade of a myocardial death receptor-mediated apoptotic pathway.

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
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kawano, H., Hayashida, T., Ohtani, H., et al. (2005). Histopathological findings of the no-reflow phenomenon following coronary intervention for acute coronary syndrome. International Heart Journal, 46, 327–332.

    Article  PubMed  Google Scholar 

  2. Jaffe, R., Charron, T., Puley, G., Dick, A., & Strauss, B. H. (2008). Microvascular obstruction and the no-reflow phenomenon after percutaneous coronary intervention. Circulation, 117, 3152–3156.

    Article  PubMed  Google Scholar 

  3. Itsuro, M., Takahito, S., Kenji, O., et al. (2000). Angiographic no-reflow phenomenon as a predictor of adverse long-term outcome in patients treated with percutaneous transluminal coronary angioplasty for first acute myocardial infarction. Journal of the American College of Cardiology, 36, 1202–1209.

    Article  Google Scholar 

  4. Grube, E., Schofer, J. J., Webb, J., et al. (2002). Evaluation of a balloon occlusion and aspiration system for protection from distal embolization during stenting in saphenous vein grafts. American Journal of Cardiology, 89, 941–945.

    Article  PubMed  Google Scholar 

  5. Patti, G., Pasceri, V., Colonna, G., et al. (2007). Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: Results of the ARMYDA-ACS randomized trial. Journal of the American College of Cardiology, 49, 1272–1278.

    Article  PubMed  CAS  Google Scholar 

  6. Pasceri, V., Patti, G., Nusca, A., et al. (2004). Randomized trial of atorvastatin for reduction of myocardial damage during coronary intervention: Results from the ARMYDA (atorvastatin for reduction of myocardial damage during angioplasty) Study. Circulation, 110, 674–678.

    Article  PubMed  CAS  Google Scholar 

  7. Scalia, R. (2005). Statins and the response to myocardial injury. American Journal of Cardiovascular Drugs, 5, 163–170.

    Article  PubMed  CAS  Google Scholar 

  8. Thielmann, M., Dörge, H., Martin, C., et al. (2002). Myocardial dysfunction with coronary microembolization: Signal transduction through a sequence of nitric oxide, tumor necrosis factor-alpha and sphingosine. Circulation Research, 90, 807–813.

    Article  PubMed  CAS  Google Scholar 

  9. Kalenikova, E. I., Gorodetskaya, E. A., Zacharova, N. V., Shechter, A. B., & Medvedev, O. S. (1998). Perindopril effects on angiotensin I elimination in lung after experimental myocardial injury induced by intracoronary microembolization in rats. Journal of Cardiovascular Pharmacology, 32, 608–615.

    Article  PubMed  CAS  Google Scholar 

  10. Bajt, M. L., Lawson, J. A., Vonderfecht, S. L., Gujral, J. S., & Jaeschke, H. (2000). Protection against Fas receptor-mediated apoptosis in hepatocytes and nonparenchymal cells by a caspase-8 inhibitor in vivo: Evidence for a postmitochondrial processing of caspase-8. Toxicological Sciences, 58, 109–117.

    Article  PubMed  CAS  Google Scholar 

  11. Schiller, N. B., Acquatella, H., Ports, T. A., et al. (1979). Left ventricular volume from paired biplane two-dimensional echocardiography. Circulation, 60, 547–555.

    PubMed  CAS  Google Scholar 

  12. Zhang, Q. Y., Ge, J. B., Chen, J. Z., et al. (2006). Mast cell contributes to cardiomyocyte apoptosis after coronary microembolization. Journal of Histochemistry and Cytochemistry, 54, 515–523.

    Article  PubMed  CAS  Google Scholar 

  13. Bell, R. M., & Yellon, D. M. (2003). Atorvastatin, administrated at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by regulating a prosurvival pathway. Journal of the American College of Cardiology, 41, 508–515.

    Article  PubMed  CAS  Google Scholar 

  14. Mensah, K., Mocanu, M. M., & Yellon, D. M. (2005). Failure to protect the myocardium against ischemia/reperfusion injury after chronic atorvastatin treatment is recaptured by acute atorvastatin treatment. Journal of the American College of Cardiology, 45, 1287–1291.

    Article  PubMed  CAS  Google Scholar 

  15. Fonarow, G. C., Wright, R. S., Spencer, F. A., et al. (2005). Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. American Journal of Cardiology, 96, 611–616.

    Article  PubMed  CAS  Google Scholar 

  16. Holeyman, C. R., & Larson, D. F. (2001). Apoptosis in the ischemic-reperfused myocardium. Perfusion, 16, 491–502.

    Google Scholar 

  17. Saikumar, P., Dong, Z., Mikhailov, V., Denton, M., Weinberg, J. M., & Venkatachalam, M. A. (1999). Apoptosis: definition, mechanism and relevance to disease. American Journal of Medicine, 107, 489–506.

    Article  PubMed  CAS  Google Scholar 

  18. Porter, A. G., & Janicke, R. U. (1999). Emerging roles of caspase-3 in apoptosis. Cell Death and Differentiation, 6, 99–104.

    Article  PubMed  CAS  Google Scholar 

  19. Krupinski, J., Lopez, E., Marti, E., & Ferrer, I. (2000). Expression of caspases and their substrates in the rat model of focal cerebral ischemia. Neurobiology of Disease, 7, 332–342.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the National Natural Science Foundation of China for financial support (Grant No. 30760262/C030313).

Author information

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi, China

    Lang Li, Qiang Su, Yan Wang, Rixin Dai, Yongguang Lu, Bo Su & Yongxiang Zhao

Authors
  1. Lang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiang Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rixin Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongguang Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bo Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yongxiang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lang Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, L., Su, Q., Wang, Y. et al. Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization. Cell Biochem Biophys 61, 399–406 (2011). https://doi.org/10.1007/s12013-011-9199-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-011-9199-z

Keywords

Search

Navigation