, Volume 15, Issue 1, pp 1–22

Therapeutic angiogenesis for myocardial ischemia revisited: basic biological concepts and focus on latest clinical trials

  • Sofoclis Mitsos
  • Konstantinos Katsanos
  • Efstratios Koletsis
  • George C. Kagadis
  • Nikolaos Anastasiou
  • Athanasios Diamantopoulos
  • Dimitris Karnabatidis
  • Dimitris Dougenis
Review Paper


Therapeutic angiogenesis is based on the premise that the development of new blood vessels can be augmented by exogenous administration of the appropriate growth factors. Over the last years, successful preclinical studies and promising results of early clinical trials have created great excitement about the potential of therapeutic angiogenesis for patients with advanced ischemic heart disease. The authors provide an overview of the biology of angiogenesis, the basic characteristics of angiogenic factors, and the different routes of their delivery. They discuss experimental studies in animal models of myocardial ischemia and outline available clinical studies on therapeutic angiogenesis for myocardial ischemia. Related safety issues are also addressed followed by a critical perspective about the future of proangiogenic therapies for ischemic cardiovascular disorders. Despite the established proof of concept and reasonable safety, however, results of the latest trials on therapeutic angiogenesis for myocardial ischemia have provided inconsistent results and the definite means of inducing clinically useful therapeutic angiogenesis remain elusive. More studies are required to gain further insights into the biology of angiogenesis and address pharmacological limitations of current approaches of angiogenic therapy. The authors hope and envisage that in the not-too-distant future, these investigative efforts will lead to important new strategies for treatment of myocardial ischemic syndromes. Means of non-invasive individualized pharmacological therapeutic neovascularization may be the next major advance in the treatment of ischaemic heart disease.


Myocardial ischemia Therapeutic angiogenesis Arteriogenesis Neovascularization Growth factors Gene therapy 



Endothelial precursor cell


Vascular endothelial growth factor


Fibroblast growth factor


Vascular endothelial growth factor receptor




Fibroblast growth factor receptor


Heparin-like glycosaminoglycans


Receptor tyrosine kinase


Monocyte chemotactic protein-1


Granulocyte-macrophage colony-stimulating factor


Hepatocyte growth factor


Platelet derived growth factor


Transforming growth factor-a/-b


Tumour necrosis factor-a


Brain-derived neurotrophic factor


Coronary artery disease


Experimental myocardial iscehima


Magnetic resonance imaging


Granulocyte colony stimulating factor


Granulocyte macrophage colony stimulating factor


Coronary artery bypass graft


Single photon emission computed tomography


Left ventricular


Left ventricular ejection fraction


Cardiac progenitor cell


Bone marrow


Bone marrow cell


Mesenchymal stem cell


Bone marrow mononuclear cell


Acute myocardial infarction


Transmyocardial laser revascularization


Percutaneous myocardial revascularization


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Sofoclis Mitsos
    • 1
  • Konstantinos Katsanos
    • 2
  • Efstratios Koletsis
    • 3
  • George C. Kagadis
    • 4
  • Nikolaos Anastasiou
    • 5
  • Athanasios Diamantopoulos
    • 2
  • Dimitris Karnabatidis
    • 2
  • Dimitris Dougenis
    • 3
  1. 1.Department of Cardiothoracic SurgeryOnassion Cardiac Surgery CenterAthensGreece
  2. 2.Department of Interventional Radiology, School of MedicinePatras University HospitalRionGreece
  3. 3.Department of Cardiothoracic Surgery, School of MedicinePatras University HospitalRionGreece
  4. 4.Department of Medical Physics, School of MedicineUniversity of PatrasPatrasGreece
  5. 5.Department of Thoracic Surgery1st IKA HospitalMelissia, AthensGreece

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