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  • Review Article
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Therapeutic angiogenesis in cardiovascular disease

Nature Reviews Drug Discovery volume 2, pages 863–872 (2003)Cite this article

Key Points

  • The development of drugs capable of stimulating revascularization of underperfused tissues remains an exciting but unrealized goal in cardiovascular medicine.

  • Recently, much has been learned about the process of new vessel growth and enlargement, the characteristics of agents that might generate new blood vessels in patients, and the nature of clinical investigations that could show efficacy and safety of this novel class of medications.

  • This review first summarizes the current state of clinical experience, and then discusses three principal issues that need to be resolved:

  • First, the identification of agents that promote growth and remodelling of larger vessels (arteriogenesis) rather than smaller vessels (true angiogenesis);

  • Second, the establishment of the required length of drug exposure in vivo and optimal means of drug delivery;

  • Third, the selection of patients, clinical trial end-points and indications for these agents.

Abstract

Despite considerable progress in the management of ischaemic cardiovascular disease during the past three decades, there remains a significant population of patients who are not served well by current treatment approaches. Stimulating revascularization in ischaemic regions is an attractive novel therapeutic strategy, and several angiogenic agents anticipated to have the potential to achieve this goal have been clinically evaluated in recent years. However, as yet none have shown sufficient efficacy to be approved. Here, we consider the key findings from the completed clinical trials of therapeutic angiogenesis in cardiovascular disease, and discuss possible changes to the way in which such agents are developed that could improve the chances of success.

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Figure 1: Therapeutic angiogenesis.
Figure 2: Arteriogenesis.
Figure 3: Drug delivery to the myocardium.

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Author information

Authors and Affiliations

  1. Departments of Medicine and Pharmacology and Toxicology, Angiogenesis Research Center and Section of Cardiology, Dartmouth Medical School, Lebanon, 03756, New Hampshire, USA

    Michael Simons

  2. Cardiovascular Research Eli Lilly & Co, Indianapolis, 46285, Indiana, USA

    J. Anthony Ware

Authors
  1. Michael Simons
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  2. J. Anthony Ware
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Corresponding author

Correspondence to Michael Simons.

Related links

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DATABASES

LocusLink

Angiopoietin-2

FGF2

FGF4

FLT-1

HIF-1α

MCP-1

PDGF-B

VEGF

FURTHER INFORMATION

Encyclopedia of Life Sciences

cardiovascular disease: epidemiology

ischemic heart disease

Glossary

CLAUDICATION

A condition in which cramping pain in the leg is induced by exercise, typically as a result of obstruction of the arteries.

ANGIOPLASTY

Catheter-based repair or unblocking of a blood vessel, such as a coronary artery.

RESTENOSIS

A re-narrowing or blockage of an artery at the same site where treatment, such as an angioplasty, has already been performed.

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Simons, M., Ware, J. Therapeutic angiogenesis in cardiovascular disease. Nat Rev Drug Discov 2, 863–872 (2003). https://doi.org/10.1038/nrd1226

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