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Therapeutic angiogenesis: protein-based therapy for coronary artery disease
Tanveer A Khan1, Frank W Sellke, Roger J Laham
1Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Dana 801, Boston, MA 02215, USA.
Insights
Therapeutic angiogenesis shows promise for ischemic heart disease, but clinical trials reveal modest results. Future research needs multi-agent therapies and improved delivery methods for better outcomes.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
Background:
- Therapeutic angiogenesis aims to improve heart function in ischemic heart disease by enhancing blood flow to the heart muscle.
- Growth factors like fibroblast growth factor and vascular endothelial growth factor have shown success in preclinical models.
Purpose of the Study:
- To evaluate the effectiveness of angiogenic therapy in treating ischemic heart disease.
- To identify factors limiting the success of current angiogenic treatments in clinical trials.
Main Methods:
- Review of preclinical studies and clinical trials on therapeutic angiogenesis for ischemic heart disease.
- Analysis of reasons for modest clinical outcomes, including endothelial dysfunction and delivery methods.
Main Results:
- Preclinical studies demonstrated significant angiogenesis with growth factors.
- Clinical trials showed only modest improvements in myocardial perfusion and patient outcomes.
- Intravascular delivery methods in Phase II trials yielded disappointing results.
Conclusions:
- Current growth factor therapies for ischemic heart disease have limited clinical success.
- Future clinical trials should focus on multi-agent angiogenic therapy and intramyocardial delivery.
- Adequately powered, randomized, double-blind, placebo-controlled trials are necessary to determine the role of angiogenesis.
Abstract:
Therapeutic angiogenesis is a promising treatment for ischaemic heart disease, particularly for patients who are not candidates for current methods of revascularisation. The goal of angiogenic therapy is the relief of symptoms of coronary artery disease and improvement of cardiac function by increasing perfusion to the ischaemic myocardium. Angiogenic cytokines such as fibroblast growth factor and vascular endothelial growth factor have been studied extensively in preclinical studies. Protein-based therapy with these growth factors has produced functionally significant angiogenesis in several animal models. Enthusiasm following these preclinical results led the way to clinical trials, which so far have shown only modest improvements in myocardial perfusion and clinical outcome. The attenuated angiogenic response to growth factor therapy observed in patients with coronary artery disease may be related to associated conditions such as endothelial dysfunction, regimens of single as opposed to multiple angiogenic agents and inefficiency of current delivery modalities, as illustrated by the disappointing results of the Phase II clinical trials using intravascular techniques of administration. The ultimate role angiogenesis will play clinically in the treatment of ischaemic heart disease will be determined by adequately powered, randomised, double-blind, placebo-controlled trials that include multi-agent angiogenic therapy and intramyocardial methods of delivery.