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  • Review Article
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Vascular endothelial growth factor in heart failure

Nature Reviews Cardiology volume 10, pages 519–530 (2013)Cite this article

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Abstract

Heart failure is a devastating condition, the progression of which culminates in a mismatch of oxygen supply and demand, with limited options for treatment. Heart failure has several underlying causes including, but not limited to, ischaemic heart disease, valvular dysfunction, and hypertensive heart disease. Dysfunctional blood vessel formation is a major problem in advanced heart failure, regardless of the aetiology. Vascular endothelial growth factor (VEGF) is the cornerstone cytokine involved in the formation of new vessels. A multitude of investigations, at both the preclinical and clinical levels, have garnered valuable information on the potential utility of targeting VEGF as a treatment option for heart failure. However, clinical trials of VEGF gene therapy in patients with coronary artery disease or peripheral artery disease have not, to date, demonstrated clinical benefit. In this Review, we outline the biological characterization of VEGF, and examine the evidence for its potential therapeutic application, including the novel concept of VEGF as adjuvant therapy to stem cell transplantation, in patients with heart failure.

Key Points

  • Heart failure is a devastating clinical entity that places a substantial burden on health-care systems, practitioners, and patients

  • Evidence indicates that dysfunctional blood vessel regulation is a key component in the pathophysiology of heart failure

  • The vascular endothelial growth factor (VEGF) family of proteins is involved in new vessel formation, endothelial cell migration and activation, stem cell recruitment, and tissue regeneration

  • The level of VEGF-A is depleted with the progression of myocardial remodelling from compensated hypertrophy to decompensated failure, reducing the capacity to generate new vessels in response to hypertrophy

  • Clinical trials of VEGF gene therapy have not, to date, demonstrated clinical benefit in patients with coronary artery disease or peripheral artery disease

  • VEGF as adjuvant therapy to stem cell transplantation is a novel concept for the treatment of heart failure

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Figure 1: The natural progression of heart failure.
Figure 2: Interactions between mammalian VEGF molecules and various receptors, and the physiological results of these interactions.
Figure 3: VEGF-A transduction pathway demonstrating the complex interplay between receptor activation and molecular mediators resulting in physiological consequence.

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Change history

  • 23 July 2013

    In Figure 1 of this article originally published online, the arrow on the left should have been pointing from the normal heart to the atrophied heart. This error has been corrected in the HTML and PDF versions of the article. The following additional sentence has also been added to the end of the legend of Figure 1: "Conversely, unloading haemodynamic stress would, theoretically, lead to atrophy."

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Authors and Affiliations

  1. Department of Internal Medicine, University of Louisville School of Medicine, 550 South Jackson Street, Louisville, 40202, KY, USA

    Ziad Taimeh

  2. Department of Internal Medicine, and Division of Cardiovascular Medicine and Institute of Molecular Cardiology, University of Louisville School of Medicine, 550 South Jackson Street, Louisville, 40202, KY, USA

    John Loughran, Emma J. Birks & Roberto Bolli

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Z. Taimeh and J. Loughran researched data for the article. All the authors contributed to the discussion of content, wrote the article, and revised/edited the manuscript before submission. Z. Taimeh and J. Loughran contributed equally and are joint first authors.

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Taimeh, Z., Loughran, J., Birks, E. et al. Vascular endothelial growth factor in heart failure. Nat Rev Cardiol 10, 519–530 (2013). https://doi.org/10.1038/nrcardio.2013.94

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