Association Between Cardiopulmonary Bypass–Induced Sirtuin-1 Suppression and Apoptosis

Authors

Bişar Amaç, Ömer Göç, Mesut Engin, Senol Yavuz
https://doi.org/10.18621/eurj.1861383
Objectives: The aim of this study is to investigate, at the molecular level, the effect of cardiopulmonary bypass (CPB) on Sirtuin-1 levels, an epigenetic-metabolic regulatory protein, and the relationship between this change and Caspase-3, one of the key executor molecules of cellular apoptosis.
Methods: Patients undergoing open heart surgery under CPB were included in the study. Sirtuin-1 and Caspase-3 levels were measured in venous blood samples taken from patients during the preoperative, intraoperative, and postoperative periods. The Wilcoxon Signed Ranks test was used to analyze differences between time points.
Results: Sirtuin-1 levels decreased significantly during the intraoperative period compared to preoperative values (Z= -6.212, P<0.001). Similarly, postoperative Sirtuin-1 levels were significantly lower compared to both the preoperative (Z= -6.229, P<0.001) and intraoperative periods (Z= -6.186, P<0.001). Caspase-3 levels showed a significant increase in the intraoperative period compared to the preoperative period (Z= −6.262, P<0.001). Postoperative Caspase-3 levels were significantly higher than both the preoperative (Z= -6.196, P<0.001) and intraoperative periods (Z= -6.203, P<0.001).
Conclusions: These findings indicate that CPB suppresses circulating Sirtuin-1 levels and that this suppression is associated with increased apoptosis. CPB-induced Sirtuin-1 inhibition may be one of the molecular mechanisms of surgical-related cellular damage. Sirtuin-1 may be considered a potential molecular target for preventing CPB-related myocardial and systemic damage.
Cardiopulmonary Bypass, Sirtuin-1, Caspase-3, Apoptosis, Molecular Perfusion

1. Zheng S, Yang L, Dai Q, Li X, Masuoka T, Lv J. Role of sirtuin 1 in depression induced coronary heart disease: Molecular pathways and therapeutic potential (Review). Biomed Rep. 2025;22(3):46. doi: 10.3892/br.2025.1924.

2. Heidari L, Ghaderian SMH, Bastami M, et al. Reverse expression pattern of sirtuin-1 and histone deacetylase-9 in coronary artery disease. Arch Physiol Biochem. 2023;129(1):46-53. doi: 10.1080/13813455.2020.1797100.

3. Doulamis IP, Tzani AI, Konstantopoulos PS, et al. A sirtuin 1/MMP2 prognostic index for myocardial infarction in patients with advanced coronary artery disease. Int J Cardiol. 2017;230:447-453. doi: 10.1016/j.ijcard.2016.12.086.

4. Raja SG, Berg GA. Impact of off-pump coronary artery bypass surgery on systemic inflammation: current best available evidence. J Card Surg. 2007;22(5):445-455. doi: 10.1111/j.1540-8191.2007.00447.x.

5. Naase H, Harling L, Kidher E, et al. Toll-like receptor 9 and the inflammatory response to surgical trauma and cardiopulmonary bypass. J Cardiothorac Surg. 2020;15(1):137. doi: 10.1186/s13019-020-01179-y.

6. Ferreira LO, Vasconcelos VW, Lima JS, et al. Biochemical Changes in Cardiopulmonary Bypass in Cardiac Surgery: New Insights. J Pers Med. 2023;13(10):1506. doi: 10.3390/jpm13101506.

7. Zakkar M, Guida G, Suleiman MS, Angelini GD. Cardiopulmonary bypass and oxidative stress. Oxid Med Cell Longev. 2015;2015:189863. doi: 10.1155/2015/189863.

8. Anselmi A, Abbate A, Girola F, et al. Myocardial ischemia, stunning, inflammation, and apoptosis during cardiac surgery: a review of evidence. Eur J Cardiothorac Surg. 2004;25(3):304-311. doi: 10.1016/j.ejcts.2003.12.003.

9. Fischer UM, Tossios P, Huebner A, Geissler HJ, Bloch W, Mehlhorn U. Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery. J Thorac Cardiovasc Surg. 2004;128(1):103-108. doi: 10.1016/j.jtcvs.2003.11.034.

10. Vachharajani VT, Liu T, Wang X, Hoth JJ, Yoza BK, McCall CE. Sirtuins Link Inflammation and Metabolism. J Immunol Res. 2016;2016:8167273. doi: 10.1155/2016/8167273.

11. Yang Y, Liu Y, Wang Y, et al. Regulation of SIRT1 and Its Roles in Inflammation. Front Immunol. 2022;13:831168. doi: 10.3389/fimmu.2022.831168.

12. Santos L, Benitez-Rosendo A, Bresque M, Camacho-Pereira J, Calliari A, Escande C. Sirtuins: The NAD+-Dependent Multifaceted Modulators of Inflammation. Antioxid Redox Signal. 2023;39(16-18):1185-1208. doi: 10.1089/ars.2023.0295.

13. Autiero I, Costantini S, Colonna G. Human sirt-1: molecular modeling and structure-function relationships of an unordered protein. PLoS One. 2008;4(10):e7350. doi: 10.1371/journal.pone.0007350.

14. Chan SH, Hung CH, Shih JY, et al. SIRT1 inhibition causes oxidative stress and inflammation in patients with coronary artery disease. Redox Biol. 2017;13:301-309. doi: 10.1016/j.redox.2017.05.027.

15. Luo G, Jian Z, Zhu Y, et al. Sirt1 promotes autophagy and inhibits apoptosis to protect cardiomyocytes from hypoxic stress. Int J Mol Med. 2019;43(5):2033-2043. doi: 10.3892/ijmm.2019.4125.

16. Eefting F, Rensing B, Wigman J, et al. Role of apoptosis in reperfusion injury. Cardiovasc Res. 2004;61(3):414-426. doi: 10.1016/j.cardiores.2003.12.023.

17. Sulpizi M, Rothlisberger U, Carloni P. Molecular dynamics studies of caspase-3. Biophys J. 2003;84(4):2207-2215. doi: 10.1016/S0006-3495(03)75026-7.

18. Kovacević M, Simić O, Jonjić N, Stifter S. Apoptosis and cardiopulmonary bypass. J Card Surg. 2007;22(2):129-134. doi: 10.1111/j.1540-8191.2006.00355.x.

19. Liu TF, McCall CE. Deacetylation by SIRT1 Reprograms Inflammation and Cancer. Genes Cancer. 2013;4(3-4):135-147. doi: 10.1177/1947601913476948.

20. Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 2004;23(12):2369-2380. doi: 10.1038/sj.emboj.7600244.

21. Cattelan A, Ceolotto G, Bova S, et al. NAD(+)-dependent SIRT1 deactivation has a key role on ischemia-reperfusion-induced apoptosis. Vascul Pharmacol. 2015;70:35-44. doi: 10.1016/j.vph.2015.02.004.

22. Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med. 2013;61:95-110. doi: 10.1016/j.freeradbiomed.2013.03.015.

There are 22 references in total.
1.
Amaç B, Göç Ömer, Engin M, Yavuz S. Association Between Cardiopulmonary Bypass–Induced Sirtuin-1 Suppression and Apoptosis. Eur Res J. 2026;12(3):339-346. doi:10.18621/eurj.1861383

Downloads

Article Information

  • File Downloads 4
  • Abstract Views 42
  • Altmetrics
  • Share
Download data is not yet available.