Enhancing the Efficacy of Angiogenic Therapies for Ischemic Diseases

Introduction

Ischemic cardiovascular diseases remain the leading cause of death worldwide, affecting hundreds of millions of patients. The prevalence of the disease is estimated to increase with the ageing of the population. Clinical management of ischemic diseases mainly focuses on prevention and treatment of atherosclerotic arterial occlusions, whereas tissue level pathology is still largely neglected, especially in terms of treatment. However, angiogenic, vascular growing therapies have been developed to improve tissue level blood flow that could directly benefit tissue recovery.

The Challenge in Stimulating the Growth of a Functional Vasculature

Stimulating the growth of a functional vasculature has turned out to be more difficult than expected, and several issues potentially limiting the clinical success of angiogenic therapies have been identified. The growth of blood vessels is guided by several different angiogenic growth factors as well as physical forces such as those elicited by blood flow. To grow blood vessels that would best serve the ischemic tissue, the right type of vessels needs to be known. Would the ischemic muscle need more arterioles to deliver oxygenated blood or capillaries to help oxygen diffusion to the tissue?

Furthermore, the induced vasculature should be able to uphold sufficient blood pressure without major leakage, but on the other hand, an increase in permeability might be needed to allow growth. Thus, how and at which stage of the growth then should the vessel wall be strengthened? Could biomaterials or tissue engineering approaches be utilized to yield more functional vessels?

Refining Therapeutic Strategies and Preclinical Methods

Initial promising results from preclinical studies faced challenges in clinical translation, requiring researchers to refine therapeutic strategies as well as preclinical methods. To overcome the bias of natural recovery in animals that could have misguided earlier studies, more clinically relevant preclinical models may be needed.

Preclinical assessment looking at the functionality of the induced neovascularization in terms of tissue survival is also highly important and may open novel understanding to what type of vascular growth the ischemic muscles would need. The length of therapy to yield stable vascular structures can be critical for efficacy as well as avoiding excessive vascular permeability and tissue oedema.

Selection and Delivery of Angiogenic Stimulus or Stimuli

The growth of blood vessels is guided by several different angiogenic growth factors. Researchers need to investigate and determine which one of the angiogenic growth factors could best initiate the whole growth cascade or whether the stimulation of several factors is needed. Moreover, the duration and delivery method of the angiogenic stimulus need to be identified for chronically ischemic tissue.

Type of Vascular Growth Stimulated or Needed by the Ischemic Tissue

To determine the type of vascular growth stimulated or needed by the ischemic tissue, researchers need to identify whether the ischemic muscle needs more arterioles to deliver oxygenated blood or capillaries to help oxygen diffusion to the tissue.

Vascular Maturation, Avoiding Excessive Permeability of Vessels

To uphold sufficient blood pressure without major leakage, the induced vasculature should be able to mature. The vessel wall should be strengthened at the appropriate stage of growth. Thus, biomaterials or tissue engineering approaches could be utilized to yield more functional vessels.

Improved Methods for and Testing of Preclinical Angiogenic Therapies

Testing of preclinical angiogenic therapies can be improved by the use of more clinically relevant preclinical models. Furthermore, preclinical assessment looking at the functionality of the induced neovascularization in terms of tissue survival is highly important.

Conclusion

The goal of the research topic is to cultivate ideas and collect new solutions to enhance the efficacy of angiogenic therapies for ischemic diseases. The purpose of this research is to distribute and call for answers to these still open questions. Submissions must include explanations regarding the potential of the selected methods to improve the efficacy of angiogenic therapies.

Originally Post From https://www.frontiersin.org/research-topics/58029/angiogenic-therapies-for-ischemic-disease

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