Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
권호 표지
DOI QR코드

DOI QR Code

Role of Ischemic Preconditioning in the Cardioprotective Mechanisms of Monomeric C-Reactive Protein-Deposited Myocardium in a Rat Model

  • Kim, Eun Na (Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Choi, Jae-Sung (Department of Thoracic and Cardiovascular Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine) ;
  • Kim, Chong Jai (Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, So Ra (Asan Laboratory of Perinatal Science, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Oh, Se Jin (Department of Thoracic and Cardiovascular Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine)
  • Received : 2020.07.15
  • Accepted : 2020.10.08
  • Published : 2021.02.05
Download PDF
⟨ Previous Next ⟩

Abstract

Background: The deposition of monomeric C-reactive protein (mCRP) in the myocardium aggravates ischemia-reperfusion injury (IRI) and myocardial infarction. Ischemic preconditioning (IPC) is known to protect the myocardium against IRI. Methods: We evaluated the effects of IPC on myocardium upon which mCRP had been deposited due to IRI in a rat model. Myocardial IRI was induced via ligation of the coronary artery. Direct IPC was applied prior to IRI using multiple short direct occlusions of the coronary artery. CRP was infused intravenously after IRI. The study included sham (n=3), IRI-only (n=5), IRI+CRP (n=9), and IPC+IRI+CRP (n=6) groups. The infarcted area and the area at risk were assessed using Evans blue and 2,3,5-triphenyltetrazolium staining. Additionally, mCRP immunostaining and interleukin-6 (IL-6) mRNA reverse transcription-polymerase chain reaction were performed. Results: In the IRI+CRP group, the infarcted area and the area of mCRP deposition were greater, and the level of IL-6 mRNA expression was higher, than in the IRI-only group. However, in the IPC+IRI+CRP group relative to the IRI+CRP group, the relative areas of infarction (20% vs. 34%, respectively; p=0.079) and mCRP myocardial deposition (21% vs. 44%, respectively; p=0.026) were lower and IL-6 mRNA expression was higher (fold change: 407 vs. 326, respectively; p=0.376), although the difference in IL-6 mRNA expression was not statistically significant. Conclusion: IPC was associated with significantly decreased deposition of mCRP and with increased expression of IL-6 in myocardium damaged by IRI. The net cardioprotective effect of decreased mCRP deposition and increased IL-6 levels should be clarified in a further study.

Keywords

References

  1. Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med 2007;357:1121-35. https://doi.org/10.1056/NEJMra071667
  2. Jennings RB, Sommers HM, Smyth GA, Flack HA, Linn H. Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog. Arch Pathol 1960;70:68-78.
  3. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13-20. https://doi.org/10.1016/S0140-6736(03)12113-7
  4. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 1986;74:1124-36. https://doi.org/10.1161/01.CIR.74.5.1124
  5. Liu Y, Downey JM. Ischemic preconditioning protects against infarction in rat heart. Am J Physiol 1992;263:H1107-12.
  6. Yellon DM, Alkhulaifi AM, Pugsley WB. Preconditioning the human myocardium. Lancet 1993;342:276-7. https://doi.org/10.1016/0140-6736(93)91819-8
  7. Armstrong S, Ganote CE. Adenosine receptor specificity in preconditioning of isolated rabbit cardiomyocytes: evidence of A3 receptor involvement. Cardiovasc Res 1994;28:1049-56. https://doi.org/10.1093/cvr/28.7.1049
  8. Deutsch E, Berger M, Kussmaul WG, Hirshfeld JW Jr, Herrmann HC, Laskey WK. Adaptation to ischemia during percutaneous transluminal coronary angioplasty: clinical, hemodynamic, and metabolic features. Circulation 1990;82:2044-51. https://doi.org/10.1161/01.CIR.82.6.2044
  9. Wu ZK, Iivainen T, Pehkonen E, Laurikka J, Tarkka MR. Ischemic preconditioning suppresses ventricular tachyarrhythmias after myocardial revascularization. Circulation 2002;106:3091-6. https://doi.org/10.1161/01.CIR.0000041430.32233.5B
  10. Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 1990;66:913-31. https://doi.org/10.1161/01.RES.66.4.913
  11. McCully JD, Uematsu M, Parker RA, Levitsky S. Adenosine-enhanced ischemic preconditioning provides enhanced cardioprotection in the aged heart. Ann Thorac Surg 1998;66:2037-43. https://doi.org/10.1016/S0003-4975(98)01042-X
  12. Wall TM, Sheehy R, Hartman JC. Role of bradykinin in myocardial preconditioning. J Pharmacol Exp Ther 1994;270:681-9.
  13. Baines CP, Goto M, Downey JM. Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium. J Mol Cell Cardiol 1997;29:207-16. https://doi.org/10.1006/jmcc.1996.0265
  14. Oh SJ, Na Kim E, Jai Kim C, Choi JS, Kim KB. The effect of C-reactive protein deposition on myocardium with ischaemia-reperfusion injury in rats. Interact Cardiovasc Thorac Surg 2017;25:260-7. https://doi.org/10.1093/icvts/ivx107
  15. Thiele JR, Habersberger J, Braig D, et al. Dissociation of pentameric to monomeric C-reactive protein localizes and aggravates inflammation: in vivo proof of a powerful proinflammatory mechanism and a new anti-inflammatory strategy. Circulation 2014;130:35-50. https://doi.org/10.1161/CIRCULATIONAHA.113.007124
  16. Li JJ, Fang CH. C-reactive protein is not only an inflammatory marker but also a direct cause of cardiovascular diseases. Med Hypotheses 2004;62:499-506. https://doi.org/10.1016/j.mehy.2003.12.014
  17. Khreiss T, Jozsef L, Potempa LA, Filep JG. Loss of pentameric symmetry in C-reactive protein induces interleukin-8 secretion through peroxynitrite signaling in human neutrophils. Circ Res 2005;97:690-7. https://doi.org/10.1161/01.RES.0000183881.11739.CB
  18. Thiele JR, Zeller J, Kiefer J, et al. A conformational change in c-reactive protein enhances leukocyte recruitment and reactive oxygen species generation in ischemia/reperfusion injury. Front Immunol 2018;9:675. https://doi.org/10.3389/fimmu.2018.00675
  19. Thompson D, Pepys MB, Wood SP. The physiological structure of human C-reactive protein and its complex with phosphocholine. Structure 1999;7:169-77. https://doi.org/10.1016/S0969-2126(99)80023-9
  20. Kim EN, Kim CJ, Kim SR, et al. High serum CRP influences myocardial miRNA profiles in ischemia-reperfusion injury of rat heart. PLoS One 2019;14:e0216610. https://doi.org/10.1371/journal.pone.0216610
  21. Basso C, Thiene G. The pathophysiology of myocardial reperfusion: a pathologist's perspective. Heart 2006;92:1559-62. https://doi.org/10.1136/hrt.2005.086959
  22. Pepys MB, Hirschfield GM, Tennent GA, et al. Targeting C-reactive protein for the treatment of cardiovascular disease. Nature 2006;440: 1217-21. https://doi.org/10.1038/nature04672
  23. Gauldie J, Richards C, Harnish D, Lansdorp P, Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A 1987;84:7251-5. https://doi.org/10.1073/pnas.84.20.7251
  24. Gwechenberger M, Mendoza LH, Youker KA, et al. Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 1999;99:546-51. https://doi.org/10.1161/01.CIR.99.4.546
  25. Tsutamoto T, Hisanaga T, Wada A, et al. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol 1998;31:391-8. https://doi.org/10.1016/S0735-1097(97)00494-4
  26. Dawn B, Xuan YT, Guo Y, et al. IL-6 plays an obligatory role in late preconditioning via JAK-STAT signaling and upregulation of iNOS and COX-2. Cardiovasc Res 2004;64:61-71. https://doi.org/10.1016/j.cardiores.2004.05.011
  27. Waldow T, Alexiou K, Witt W, et al. Protection against acute porcine lung ischemia/reperfusion injury by systemic preconditioning via hind limb ischemia. Transpl Int 2005;18:198-205. https://doi.org/10.1111/j.1432-2277.2004.00005.x
  28. Smart N, Mojet MH, Latchman DS, Marber MS, Duchen MR, Heads RJ. IL-6 induces PI 3-kinase and nitric oxide-dependent protection and preserves mitochondrial function in cardiomyocytes. Cardiovasc Res 2006;69:164-77. https://doi.org/10.1016/j.cardiores.2005.08.017
  29. Harkin DW, Barros D'Sa AA, McCallion K, Hoper M, Campbell FC. Ischemic preconditioning before lower limb ischemia: reperfusion protects against acute lung injury. J Vasc Surg 2002;35:1264-73. https://doi.org/10.1067/mva.2002.121981
  30. Kitsis RN, Jialal I. Limiting myocardial damage during acute myocardial infarction by inhibiting C-reactive protein. N Engl J Med 2006;355:513-5. https://doi.org/10.1056/NEJMcibr063197