Therapeutic angiogenesis in coronary artery disease: a review of mechanisms and current approaches

ABSTRACT

Introduction

Despite tremendous advances, the shortcomings of current therapies for coronary disease are evidenced by the fact that it remains the leading cause of death in many parts of the world. There is hence a drive to develop novel therapies to tackle this disease. Therapeutic approaches to coronary angiogenesis have long been an area of interest in lieu of its incredible, albeit unrealized potential.

Areas covered

This paper offers an overview of mechanisms of native angiogenesis and a description of angiogenic growth factors. It progresses to outline the advances in gene and stem cell therapy and provides a brief description of other investigational approaches to promote angiogenesis. Finally, the hurdles and limitations unique to this particular area of study are discussed.

Expert opinion

An effective, sustained, and safe therapeutic option for angiogenesis truly could be the paradigm shift for cardiovascular medicine. Unfortunately, clinically meaningful therapeutic options remain elusive because promising animal studies have not been replicated in human trials. The sheer complexity of this process means that numerous major hurdles remain before therapeutic angiogenesis truly makes its way from the bench to the bedside.

KEYWORDS:

• Therapeutic
• angiogenesis
• therapeutic angiogenesis
• coronary
• coronary artery disease
• growth factors
• stem cells
• gene therapy

Article highlights

• Current approaches to treatment rely heavily on mechanically overcoming or bypassing sites of obstruction to optimize coronary blood flow. These approaches address issues at a local epicardial level, doing nothing to address arguably the more important microvascular disease.

• Effective means of inducing therapeutic angiogenesis could address these issues and truly emerge as the paradigm shift that cardiovascular medicine awaits.

• A common theme in this arena has been the poor replication of promising experimental and animal trial results in the diseased vasculature.

• Growth factor administration, gene therapy, and stem cell therapy have been the major therapeutic approaches studied. More novel approaches including small molecules, optogenetics, and extracellular vesicles have gained interest in recent years.

• Numerous difficulties unique to this area include heterogeneous study data, difficulty in achieving and sustaining adequate levels of growth factors at the target site, optimizing the sequence of growth factor delivery to optimize vessel maturation as well as biological concerns of aberrant vascular proliferation in non-target tissues to name a few.

• Going forward, simultaneous multi-specialty advances in oncology, genetic engineering, bioengineering, and vascular medicine could help overcome a number of the hurdles faced today.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

One referee has worked on miR-93 for the treatment of peripheral arterial disease. Peer reviewers in this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.