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Updated: May 14, 2026
Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Mechanistic, technical, and clinical perspectives in therapeutic stimulation of coronary collateral development by
1Cardium Therapeutics, Inc., San Diego, California 92130, USA. grubanyi@cardiumthx.com
Abstract:
Stimulation of collateral vessel development in the heart by angiogenic growth factor therapy has been tested in animals and humans for almost two decades. Discordance between the outcome of preclinical studies and clinical trials pointed to the difficulties of translation from animal models to patients. Lessons learned in this process identified specific mechanistic, technical, and clinical hurdles, which need to be overcome. This review summarizes current understanding of the mechanisms leading to the establishment of a functional coronary collateral network and the biological processes growth factor therapies should stimulate even under conditions of impaired natural adaptive vascular response. Vector delivery methods are recommended to maximize angiogenic gene therapy efficiency and reduce side effects. Optimization of clinical trial design should include the choice of clinical end points which provide mechanistic proof-of-concept and also reflect clinical benefits (e.g., surrogates to assess increased collateral flow reserve, such as myocardial perfusion imaging). Guidelines are proposed to select patients who may respond to the therapy with high(er) probability. Both short and longer term strategies are outlined which may help to make therapeutic angiogenesis (TA) work in the future.
Insights
Therapeutic angiogenesis aims to stimulate heart vessel growth but faces challenges translating animal success to human trials. Strategies include optimizing gene therapy delivery and clinical trial design for better patient outcomes.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Translational Science
Background:
- Angiogenic growth factor therapy for coronary collateral vessel development has shown a significant discordance between preclinical animal studies and human clinical trials.
- This discrepancy highlights the inherent difficulties in translating findings from animal models to human patients, necessitating a deeper understanding of underlying mechanisms.
Purpose of the Study:
- To review the current understanding of mechanisms governing functional coronary collateral network establishment.
- To identify biological processes crucial for growth factor therapies, especially in cases of impaired natural vascular adaptation.
- To propose strategies for overcoming hurdles in therapeutic angiogenesis.
Main Methods:
- Review of existing literature on coronary collateral development and therapeutic angiogenesis.
- Analysis of mechanistic, technical, and clinical challenges in translating preclinical findings.
- Evaluation of vector delivery methods for angiogenic gene therapy.
- Assessment of clinical trial design optimization, including endpoint selection and patient stratification.
Main Results:
- Current understanding of coronary collateral network formation mechanisms is summarized.
- Vector delivery methods are recommended to enhance angiogenic gene therapy efficiency and minimize side effects.
- Optimization of clinical trial design, including proof-of-concept endpoints and patient selection, is crucial for success.
Conclusions:
- Therapeutic angiogenesis (TA) requires overcoming specific mechanistic, technical, and clinical hurdles for successful clinical application.
- Improved vector delivery and optimized clinical trial designs, focusing on functional outcomes and patient selection, are key to making TA effective.
- Future strategies involve both short-term and long-term approaches to advance the field of therapeutic angiogenesis for cardiovascular diseases.
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