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

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Abstract

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.

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Abbreviations

EPC:

Endothelial precursor cell

VEGF:

Vascular endothelial growth factor

FGF:

Fibroblast growth factor

VEGFR:

Vascular endothelial growth factor receptor

NP/NRP:

Neuropilin

FGFR:

Fibroblast growth factor receptor

HLGAG:

Heparin-like glycosaminoglycans

RTK:

Receptor tyrosine kinase

MCP-1:

Monocyte chemotactic protein-1

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HGF:

Hepatocyte growth factor

PDGF:

Platelet derived growth factor

TGF-a/TGF-b:

Transforming growth factor-a/-b

TNF-a:

Tumour necrosis factor-a

BDNF:

Brain-derived neurotrophic factor

CAD:

Coronary artery disease

EMI:

Experimental myocardial iscehima

MRI:

Magnetic resonance imaging

G-CSF:

Granulocyte colony stimulating factor

GM-CSF:

Granulocyte macrophage colony stimulating factor

CABG:

Coronary artery bypass graft

SPECT:

Single photon emission computed tomography

LV:

Left ventricular

LVEF:

Left ventricular ejection fraction

CPC:

Cardiac progenitor cell

BM:

Bone marrow

BMC:

Bone marrow cell

MSC:

Mesenchymal stem cell

BM-MNC:

Bone marrow mononuclear cell

AMI:

Acute myocardial infarction

TMR:

Transmyocardial laser revascularization

PMR:

Percutaneous myocardial revascularization

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Acknowledgments

This work was supported in part by a University of Patras, Research Programme “K. Karatheodori”. Sofoclis Mitsos was also supported by a scholarship for doctoral studies of Alexander S. Onassis Public Benefit Foundation, Greece.

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Onassion Cardiac Surgery Center, Athens, Greece

    Sofoclis Mitsos

  2. Department of Interventional Radiology, School of Medicine, Patras University Hospital, 26504, Rion, Greece

    Konstantinos Katsanos, Athanasios Diamantopoulos & Dimitris Karnabatidis

  3. Department of Cardiothoracic Surgery, School of Medicine, Patras University Hospital, 26504, Rion, Greece

    Efstratios Koletsis & Dimitris Dougenis

  4. Department of Medical Physics, School of Medicine, University of Patras, 26504, Patras, Greece

    George C. Kagadis

  5. Department of Thoracic Surgery, 1st IKA Hospital, Terma Zaimi, 15127, Melissia, Athens, Greece

    Nikolaos Anastasiou

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  1. Sofoclis Mitsos
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Correspondence to Konstantinos Katsanos.

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Mitsos, S., Katsanos, K., Koletsis, E. et al. Therapeutic angiogenesis for myocardial ischemia revisited: basic biological concepts and focus on latest clinical trials. Angiogenesis 15, 1–22 (2012). https://doi.org/10.1007/s10456-011-9240-2

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  • DOI: https://doi.org/10.1007/s10456-011-9240-2

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