Ischemic cardiovascular diseases remain the leading cause of death worldwide with hundreds of millions of patients currently affected and the prevalence of the disease estimated to increase with aging of the population. Clinical management of ischemic diseases to date mainly focuses on prevention and treatment of atherosclerotic arterial occlusions whereas the tissue level pathology is still largely neglected, especially in terms of treatment.

Angiogenic, vascular growing therapies have been developed to improve tissue level blood flow that could directly benefit tissue recovery. However, stimulating the growth of a functional vasculature has turned out to be more difficult than expected.

The initial promising results from preclinical studies faced challenges in clinical translation. Thus, researchers were required to refine therapeutic strategies as well as preclinical methods.

Several issues still 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. Which one of the angiogenic growth factors could best initiate the whole growth cascade or is the stimulation of several factors needed?

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?

The induced vasculature should also 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. So, how and at which stage of the growth then should the vessel wall be strengthened? And, could biomaterials or tissue engineering approaches be utilized to yield more functional vessels?

Furthermore, the use of more clinically relevant preclinical models may be needed to overcome the bias of natural recovery in animals that could have misguided earlier studies. 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.

Finally, how long should the angiogenic stimulus be and what would be the best way to deliver the stimulation to chronically ischemic tissue?

The goal of this research topic is to call for answers to these still open questions.

The purpose of this research topic is to distribute and cultivate ideas on how to enhance the efficacy of angiogenic therapies for ischemic diseases. Original research articles, systematic reviews/meta-analyses, and perspective articles pertaining to the following themes are welcomed:

• Selection and delivery of angiogenic stimulus or stimuli

• Type of vascular growth stimulated or needed by the ischemic tissue

• Vascular maturation, avoiding excessive permeability of vessels

• Improved methods for and testing of preclinical angiogenic therapies

Submissions must include explanations regarding the potential of the selected methods to improve efficacy of angiogenic therapies

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Frontiers in Bioengineering and Biotechnology

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