

A protein involved in the development of blood vessels in the womb could provide a promising target for new drugs to treat abdominal aortic aneurysms (AAAs), according to research funded by the us published today in the Journal of Clinical Investigation.
Researchers, led by Dr Nicola Smart at the University of Oxford, identified that the protein, Thymosin β4, is also vital to protect the health of blood vessels throughout life. They hope that drugs which target Thymosin β4 could help to prevent or even reverse damage to blood vessels seen in people with an AAA.
Lack of treatments for deadly condition
There are no drugs currently available to treat AAA, a balloon-like swelling in the abdominal portion of the aorta (the body’s biggest blood vessel). The only treatment available is a high-risk surgery, but this is only offered to patients with the largest aneurysms.If an AAA becomes too large, it can burst causing massive internal bleeding. Up to 90 per cent of people with a ruptured AAA die and the condition is responsible for at least 3,000 deaths in the UK each year.
A vital role for Thymosin β4
The researchers found that Thymosin β4 is essential to keep the smooth muscle cells in the wall of the aorta in their healthy state. The loss of smooth muscle cells is commonly seen in the aortic walls of people with AAA.
When the team looked at samples of aortic tissue from people with an AAA they found that the vessel walls looked identical to the aortas of mice missing Thymosin β4. Mice missing the protein were also more prone to developing aneurysms.
The researchers identified that Thymosin β4 interacts with another protein, Low-density lipoprotein receptor-related protein 1 (LRP1), in both mice and humans. Previous research has found that mutations in the gene for LRP1 are a risk factor for developing AAA.
They found that Thymosin β4 was needed to regulate the activity of LRP1. Without it, LRP1 became overactive which caused damage to smooth muscle cells. When they treated the mice missing Thymosin β4 with a drug that reduced LRP1 activity, the researchers found that they were able to reverse some of the damage that had been caused.
Professor James Leiper, our Associate Medical Director, said:
“AAAs are a devastating condition for which, in many cases, the only option is high-risk surgery. New treatments are desperately needed and could help to save thousands of lives.
“While it’s still early days, this research offers much needed hope for the development of treatments for AAA.”
The research was also supported by the Oxford Medical Research Council Doctoral Training Partnership.
Find out more about abdominal aortic aneurysms