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Angiogenic therapy for cardiac repair based on protein delivery systems

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Abstract

Cardiovascular diseases remain the first cause of morbidity and mortality in the developed countries and are a major problem not only in the western nations but also in developing countries. Current standard approaches for treating patients with ischemic heart disease include angioplasty or bypass surgery. However, a large number of patients cannot be treated using these procedures. Novel curative approaches under investigation include gene, cell, and protein therapy. This review focuses on potential growth factors for cardiac repair. The role of these growth factors in the angiogenic process and the therapeutic implications are reviewed. Issues including aspects of growth factor delivery are presented in relation to protein stability, dosage, routes, and safety matters. Finally, different approaches for controlled growth factor delivery are discussed as novel protein delivery platforms for cardiac regeneration.

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Abbreviations

Ang:

Angiopoietin

C-GSF:

Colony granulocyte stimulating factor

CHF:

Chronic heart failure

cMLCK:

Cardiac-specific myosin light-chain kinase

CVD:

Cardiovascular diseases

EC:

Endothelial cell

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

EPC:

Endothelial progenitor cell

EPO:

Erythropoietin

ErbB:

NRG tyrosine kinase receptor

FDA:

US Food and drug administration

FGF:

Fibroblast growth factor

FGF-1:

Acidic fibroblast growth factor

FGF-2:

Basic fibroblast growth factor

FGFR:

FGF tyrosine kinase receptor

G-CSF:

Granulocyte colony-stimulating factor

GF:

Growth factor

HGF:

Hepatocyte growth factor

HIF-1α:

Hypoxia inducible factor-1α

HSPGs:

Heparan sulfate proteoglycans

IHD:

Ischemic heart disease

LAD:

Left anterior descending coronary artery

LVEF:

Left ventricle ejection fraction

MCP-1:

Monocyte chemoattractant protein-1

MMPs:

Matrix metalloproteinases

NO:

Nitric oxide

NRG:

Neuregulin

PDGF:

Platelet-derived growth factor

PDGFR:

PDGF tyrosine kinase receptor

PEG:

Poly(ethylene glycol)

PEO:

Poly(ethylene oxide)

Shh:

Sonic hedgehog

TGF-β:

Transforming growth factor-β

Tie:

Ang tyrosine kinase receptor

TNF-α:

Tumor necrosis factor-α

VEGF:

Vascular endothelial growth factor

VEGFR:

VEGF tyrosine kinase receptor

VSMC:

Vascular smooth muscle cell

WHF:

World Heart Federation

WHO:

World Health Organization

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Acknowledgments

This work was supported in part by Instituto de Salud Carlos III (ISCIII PI050168, PI10/01621, CP09/00333 and ISCIII-RETIC RD06/0014), Ministerio de Ciencia e Innovación (PLE2009-0116 and PSE SINBAD, PSS 0100000-2008-1), Gobierno de Navarra (Departamento de Educación), Comunidad de Trabajo de los Pirineos (CTP), European Union Framework Project VII (INELPY), Agencia Española de Cooperación Internacional para el Desarrollo (AECID), Caja de Ahorros de Navarra (Programa Tu Eliges: Tu Decides) and the “UTE project CIMA”.

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Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra, Irunlarrea 1, 31080, Pamplona, Spain

    F. R. Formiga, E. Tamayo, T. Simón-Yarza & M. J. Blanco-Prieto

  2. Hematology Service and Area of Cell Therapy, Clínica Universidad de Navarra, Foundation for Applied Medical Research, University of Navarra, Pamplona, Spain

    B. Pelacho & F. Prósper

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  1. F. R. Formiga
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  2. E. Tamayo
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  3. T. Simón-Yarza
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  6. M. J. Blanco-Prieto
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Correspondence to M. J. Blanco-Prieto.

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Formiga, F.R., Tamayo, E., Simón-Yarza, T. et al. Angiogenic therapy for cardiac repair based on protein delivery systems. Heart Fail Rev 17, 449–473 (2012). https://doi.org/10.1007/s10741-011-9285-8

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