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Updated: Jun 26, 2026
Assessing Therapeutic Angiogenesis in a Murine Model of Hindlimb Ischemia
Published on: June 8, 2019
Therapeutic angiogenesis in diabetes and hypercholesterolemia: influence of oxidative stress
Munir Boodhwani1, Frank W Sellke
1Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada.
Insights
Therapeutic angiogenesis shows promise for non-revascularizable coronary artery disease (CAD). However, clinical trials often fail due to the patient
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Molecular Biology
Background:
- Advanced coronary artery disease (CAD) often presents as non-revascularizable.
- Therapeutic angiogenesis aims to improve myocardial perfusion but faces clinical translation challenges.
- Preclinical successes in angiogenesis contrast with clinical trial failures, suggesting a need to address the patient's cellular environment.
Purpose of the Study:
- To review the angiogenic process in the context of advanced CAD.
- To explore pathophysiologic and molecular mechanisms impairing angiogenic response.
- To discuss substrate-modifying interventions to enhance angiogenic therapy.
Main Methods:
- Review of preclinical and clinical studies on therapeutic angiogenesis.
- Analysis of molecular and cellular mechanisms in endothelial dysfunction, hypercholesterolemia, and diabetes.
- Focus on the role of oxidative stress in impaired angiogenesis.
Main Results:
- Clinical angiogenesis therapies have not met preclinical expectations.
- Endothelial dysfunction, hypercholesterolemia, and diabetes create an anti-angiogenic environment in CAD patients.
- Oxidative stress is a key factor contributing to impaired angiogenic responses.
Conclusions:
- Modifying the pro-angiogenic substrate is crucial for successful therapeutic angiogenesis in CAD.
- Targeting disease-specific abnormalities can enhance the efficacy of protein-, gene-, or cell-based angiogenic therapies.
- Substrate-modifying agents offer a potential strategy to improve outcomes in patients with non-revascularizable CAD.
Abstract:
Despite significant improvements in the medical, percutaneous, and surgical management, numerous patients are first seen with non-revascularizable coronary artery disease (CAD). The growth of new blood vessels to improve myocardial perfusion (i.e., therapeutic angiogenesis) is an attractive treatment option for these patients. However, the successes of angiogenic therapy, observed in preclinical studies, have not been realized in clinical trials. Increasing evidence suggests that this discrepancy between animal and human studies may be due to the nature of the substrate, or the molecular and cellular environment within which the angiogenic agent acts. Antiangiogenic influences, including endothelial dysfunction, hypercholesterolemia, and diabetes, are present in virtually all patients with advanced CAD. Recent studies have better characterized the abnormalities associated with these disease states, providing novel targets for intervention. These substrate-modifying interventions can potentially enhance the response to protein-, gene-, or cell-based angiogenic therapy. In this review, we discuss key aspects of the angiogenic process and the pathophysiologic and molecular mechanisms that contribute to an impaired angiogenic response in the setting of endothelial dysfunction, hypercholesterolemia, and diabetes, with a focus on the role of oxidative stress. Last, we briefly explore substrate modifying agents that have been evaluated in preclinical and clinical studies to improve the angiogenic response.
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