About this Research Topic
Development of atherosclerosis leads to narrowing/ blockage of large and medium-size arteries that restricts blood supply to the downstream tissue. Ischaemic disease, including ischaemic heart disease and critical limb ischaemia, presents a huge medical and economic burden to modern society. Reopening or replacing the blocked artery (by percutaneous intervention with stenting or by vascular bypass surgery) are effective strategies to restore perfusion in the ischaemic tissue. However, these invasive interventions are typically employed at late-stage disease when critical ischaemia has been established. Notably, there is a large group of patients who are not eligible/suitable for surgical intervention, either because of the complex vascular pathology or lack of suitable autologous vascular grafts. Crucially, validated early intervention for ischaemic disease is lacking.
The concept of therapeutic angiogenesis was developed in this context with the aim to promote reperfusion in the ischaemic tissue via stimulation of angiogenesis. A range of therapeutic approaches have been explored to encourage angiogenesis around and in the ischaemic tissue that includes delivering proangiogenic factors, proangiogenic gene therapies, and stem cell-based therapies. Unfortunately, therapeutic benefit is marginal and elusive with no successful clinical translation so far.
From the haemodynamic point of view, it is almost impossible to restore the blood supply by replacing a blocked artery with a number of microvessels (via angiogenesis). According to Poiseuille’s Law, Q= (Δ𝑃𝜋𝑅4)/( 8𝜇𝐿), the ability of a blood vessel to conduct blood flow is proportional to the 4th power of its radius. That is to say, it will require 1.6 billion new microvessels (at a diameter of 10µm) to replace a blocked artery (at a diameter of 2mm), which is clearly unrealistic.
Alternatively, the human body does reserve the ability to grow collateral arteries, in response to ischaemia or increased metabolic demand, to divert blood to the affected tissue. Indeed, a close analysis of those therapeutic angiogenesis studies that did have positive outcomes often demonstrated significant collateral growth along with angiogenesis, revealing that some pro-angiogenic factors also stimulate arteriogenesis and collateral growth. Nevertheless, the availability of focused research on mechanisms of arteriogenesis and collateralisation are insufficient despite the great potential in therapeutics. This may be partly due to the lack of research tools to image, quantify and analyse the remodelling of the arterial network, including vessel diameter, length, networking, haemodynamics and the ultimate impact of intervention on downstream perfusion. This focused research topic aims to promote research publication in the area of arteriogenesis and collateral remodelling in ischaemic disease and is open to either original research papers or review articles. We are particularly keen to receive articles that focus on the following areas:
1. Development and application of novel imaging technologies, models, and computational modelling for studying vascular network remodelling, in particular arteriogenesis and collateral growth, and its impact on perfusion.
2. Investigating the cellular and molecular mechanisms of vascular network remodelling following acute or chronic ischaemia.
3. Investigating the potential impact of cardiovascular conditions and medication (e.g. diabetes, hypertension, and vascular calcification, etc.) on haemodynamics, collateral growth, and tissue perfusion.
4. Identifying new therapeutic strategies and potential drug targets that regulate arteriogenesis and collateral remodelling in acute or chronic ischaemic disease.
We welcome all types of manuscripts, including: original basic science reports, review articles, methodology papers, translational research, and clinical studies.
Keywords: Ischaemia, perfusion, arteriogenesis, collateral artery, vascular network remodelling
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