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Is activation of coronary venous cells the key to cardiac regeneration?

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 528–530 (2008)Cite this article

Myocardial regeneration for endogenous cardioprotection is an attractive treatment option. The mechanisms by which cardiac cell therapy could induce myocardial regeneration and, ultimately, recovery of the failing heart, however, remain an enigma. As the quest for a better understanding of cardiac regeneration continues, we believe alternatives beyond stem cell research should be considered. In this Viewpoint we focus on the potential to use innate mechanisms that are active during cardiac development. These mechanisms lie dormant in the adult, but can be reactivated during adult life. Regression into embryonic or fetal molecular pathways is seen during physiologic adaptation (i.e. cardiac hypertrophy) and in disease processes such as neoplasia and metastasis. Despite obvious potential, recapitulation of 'epigenetic' embryonic pathways as a means for regeneration of the adult failing heart has been neglected until recently.1

Mechanotransduction is a simple approach that uses hemodynamic force to activate coronary venous vasculature, and is a viable alternative to mainstream research to recover jeopardized myocardium. Pressure-controlled intermittent coronary sinus occlusion (PICSO) is a clinically available coronary sinus intervention with known cardioprotective effects. This technique seems to have the potential to reactivate embryonic pathways through the induction of shear stress and pulsatile stretch of blood flow in the coronary microcirculation. PICSO works by allowing a pressure wave front to enter the ischemic coronary bed by redistribution of blood in the myocardium during intermittent occlusion of the coronary sinus. After the systolic pressure reaches a plateau, the occlusion is released allowing drainage. Concomitant to this elevation in venous pressure is the increase in the arterial pressure in the occluded coronary artery (the increase of collateral flow), which improves perfusion in border zones resulting in a considerable reduction in infarct size. PICSO, with its confirmed cytoprotective effects in the ischemic heart, acts only by manipulating coronary venous blood flow; retroperfusion of arterial blood—the suggested benefit in other coronary sinus interventions (see Supplementary Figure 1 online)2—does not occur with PICSO. There has been speculation for some time that improvement in collateral flow is an important parameter in the reduction of infarct size by use of PICSO.3 Experimental PICSO studies have demonstrated significant upregulation in vascular endothelial growth factor (VEGF) and hemoxygenase expression,4 effects otherwise difficult to achieve without gene or stem cell therapy. The vasodilatatory and regenerative effects of these molecules seem to be essential in the salvage of ischemic border zones, as seen in a range of animal models.5

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References

  1. Mohl W (2007) Embryonic recall: myocardial regeneration beyond stem cell transplantation. Wien Klin Wochenschr 119: 333–336

    Article  Google Scholar 

  2. Beck CS et al. (1946) Revascularization of heart by graft of systemic artery into coronary sinus. JAMA 137: 436–445

    Article  Google Scholar 

  3. Mohl W et al. (1984) Reduction of infarct size induced by pressure-controlled intermittent coronary sinus occlusion. Am J Cardiol 53: 923–928

    Article  CAS  Google Scholar 

  4. Weigel G et al. (2007) Beck and back: a paradigm change in coronary sinus interventions—pulsatile stretch on intact coronary venous endothelium. J Thorac Cardiovasc Surg 133: 1581–1587

    Article  Google Scholar 

  5. Syeda B et al. (2004) The salvage potential of coronary sinus interventions: meta-analysis and pathophysiologic consequences. J Thorac Cardiovasc Surg 127: 1703–1712

    Article  Google Scholar 

  6. Banai S et al. (2007) Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris: a prospective, open-label, multicenter, safety feasibility first-in-man study. J Am Coll Cardiol 49: 1783–1799

    Article  Google Scholar 

  7. Zheng W et al. (2001) Mechanisms of coronary angiogenesis in response to stretch: role of VEGF and TGF-beta. Am J Physiol Heart Circ Physiol 280: H909–H917

    Article  CAS  Google Scholar 

  8. Groenendijk BCW et al. (2005) Changes in shear stress-related gene expression after experimentally altered venous return in the chicken embryo. Circ Res 96: 1291–1298

    Article  CAS  Google Scholar 

  9. Grunewald M et al. (2006) VEGF-induced adult neovascularization: recruitment, retention and role of accessory cells. Cell 124: 175–189

    Article  CAS  Google Scholar 

  10. Verma S et al. (2002) Fundamentals of reperfusion injury for the clinical cardiologist. Circulation 105: 2332–2336

    Article  Google Scholar 

  11. Papapetropoulos A et al. (1997) Nitric oxide production contributes to the angiogenic properties of vascular endothelial growth factor in human endothelial cells. J Clin Invest 100: 3131–3139

    Article  CAS  Google Scholar 

  12. Mohl W et al. (1988) Clinical evaluation of pressure-controlled intermittent coronary sinus occlusion: randomized trial during coronary artery surgery. Ann Thorac Surg 46: 192–201

    Article  CAS  Google Scholar 

  13. Kasahara H et al. (2007) Do long term effects after PICSO endorse the potential of cardiac regeneration after acute myocardial infarction? Wien Klin Wochenschr 119 (Suppl 1): 23–26

    CAS  PubMed  Google Scholar 

  14. Mohl W et al. (2008) Myocardial protection via the coronary sinus: long term effects of intermittent coronary sinus occlusion as adjunct to reperfusion in acute myocardial infarction. Circ J. 72: 526–533

    Article  Google Scholar 

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Authors and Affiliations

  1. W Mohl is Professor of Surgery at the Department of Cardiothoracic Surgery, and G Maurer is Professor of Medicine at the Department of Cardiology, S Mina is a Clinical Affairs Manager/Development Engineer at the Biomedical Engineering Department, D Milasinovic is a medical student, the University of Vienna General Hospital of Vienna, Austrian Research Centers GmbH, Vienna, Austria,

    Werner Mohl, Stefan Mina, Dejan Milasinovic & Gerald Maurer

  2. H Kasahara is Assistant Professor at the Department of Cardiothoracic Surgery, Keio University School of Medicine, Tokyo, Japan,

    Hirofumi Kasahara

  3. S Wei is a Cardiac Surgical Resident at the Department of Cardiovascular Surgery, China PLA General Hospital, Beijing, China.,

    Sheng Wei

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  1. Werner Mohl
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  4. Hirofumi Kasahara
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Correspondence to Werner Mohl.

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Competing interests

W Mohl is shareholder and consultant to Miracor, a company engaged in developing the PICSO technology. The other authors declared no competing interests.

Supplementary information

Supplementary Figure 1

Pressure tracing during pressure-controlled intermittent coronary sinus occlusion (PICSO). (DOC 97 kb)

Supplementary Figure 2

Incidence of reinfarction and freedom of MACE in patients with acute coronary syndromes. (DOC 25 kb)

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Mohl, W., Mina, S., Milasinovic, D. et al. Is activation of coronary venous cells the key to cardiac regeneration?. Nat Rev Cardiol 5, 528–530 (2008). https://doi.org/10.1038/ncpcardio1298

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