Scientists have found the key to angiogenesis, or how blood vessels regenerate, paving the way for new treatments for conditions that cause a restriction in our blood supply.
Ischemia is the critical decrease in oxygenated blood supply to an organ or the tissues of the extremities, which often leads to ulcers and gangrene.
Narrowed arteries in the muscles of the heart are one of the central causes of serious cardiac pathologies, such as cardiac ischemia, or ischemic heart disease.
Despite the progress made in the prevention of risk factors and the management of complications, these pathologies have staggering mortality rates. Cardiac ischemia is the leading cause of death worldwide.
Angiogenesis: Biological Process Involved in Both Health and Sickness
Angiogenesis is the natural process that enables the formation of new blood vessels or “neovascularization” from a pre-existing vascular network.
Angiogenesis is particularly indispensable during many vital physiological processes such as embryonic development, tissue repair, and placental implantation but can also contribute to some more detrimental processes within the human body.
Like any other tissue, cancerous tissue needs nutrients and oxygen carried by blood vessels. As a result, angiogenesis also plays a crucial role in the formation of tumor growth and metastases.
The body’s response to this is a restriction in blood flow by setting up a process of tissue and vascular regeneration. Unfortunately, this doesn’t always work well, which is clearly evident in the millions of deaths recorded every year due to this medical issue.
Now, a new discovery provides insights into the mechanism of angiogenesis, which could help develop treatment strategies to stimulate tissue regeneration and greatly reduce the risk of ischemia and cardiovascular disease.
Shedding new Light on the Mechanism of Angiogenesis
A team of researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) have discovered a key signaling pathway at the heart of angiogenesis.
Current efforts to treat ischemia focus on delivering what’s known as a vascular endothelial growth factor (VEGF) to ischemic tissues in the body. However, neither treatment has yet yielded any apparent benefits.
“Functional vessels need to have a lumen; a pipe-like opening that allows oxygenated blood and nutrients to travel through the body,” said Dr. Masanobu Komatsu, co-author of the study, “and VEGF alone cannot fully support the formation of such a vessel structure.”
The SBP team discovered that the protein (R-Ras) activates the signaling pathway Akt, allowing the formation of a lumen (the hollow tubular structure) of new blood vessels, and suggested this step as complementary to VEGF.
“First, VEGF activates Akt to induce endothelial cells to sprout. Then, R-Ras activates Akt to induce lumen formation,” explains Fangfei Li, lead author of the study. “The second step involving Akt activation by R-Ras stabilizes the microtubule cytoskeleton in endothelial cells, creating a steady architecture that promotes lumen formation.”
The next step for Dr. Komatsu and his research team is to attempt to prompt Akt signaling either via VEGF or gene therapy.
As it stands, the foundation of this new approach to vascular issues has been established, with other developments such as advanced organic 3D printing aiding in the gradual defeat of this medical problem.
The findings of the study were published in the journal Nature Communications.
If researchers can create lumens by isolating certain proteins and thus enable successful VEGF treatment of ischemia, what stops this research from being the beginning of the end of heart disease?