Why is it that some patients with heart disease are less likely to die from it than others? Scientists believe the answer may partly lie in a DIy repair mechanism that kicks in when blood flow to the heart is reduced. In response, the heart starts to grow small new blood vessels called collaterals.
Around the world, scientists are developing ways to boost these collateral vessels, paving the way for new treatments that could end the misery of angina ( chest pain caused by narrowed or blocked blood vessels supplying the heart), avoid surgery and reduce the damage caused by a heart attack.
For years, patients with heart disease and angina have been told that, if drugs don’t work, the best option is an operation to unblock the narrowed vessels that are causing symptoms.
This involved either inserting a tube called a stent to hold the vessel open, or bypass surgery — where surgeons take a blood vessel from the arm or leg and sew it into place on either side of the blockage to divert blood.
Explaining how collaterals work, Professor Tony Gershlick, a consultant cardiologist at University hospitals of Leicester NhS Trust, says: ‘ Collaterals are small blood vessels running alongside the main coronary arteries to the heart.
‘If you block a stream, the water can still run in small tributaries round the outside.’ he adds that collaterals work in a similar way.
‘ They’re probably present in everyone to some degree — and how many you have is probably genetically determined — but they’re not normally carrying a lot of blood. It’s more like a trickle.’
These collateral vessels have little to do under normal circumstances because the three main coronary arteries carry the main flow of blood into the heart muscle. But if one of them becomes blocked, this slowly starves the heart of oxygen.
In response, blood vessel cells in the heart switch on a ‘master regulator’ molecule called hIF1A, or hypoxiainducible factor 1alpha.
In turn, this releases various growth factors, chemicals that make existing collateral vessels grow larger and also trigger new blood vessels to sprout from the main arteries — a process known as angiogenesis. These redirect the flow around the blockage and keep the heart healthy.
This chimes with the discovery that exercise, which causes a temporary drop in oxygen in the heart and also pushes more blood through existing collateral vessels, can trigger the growth of new collaterals, too.
But it’s a slow process, especially in the heart, and often isn’t fast or efficient enough to compensate for blocked arteries. And people with heart disease may not be able to safely exercise enough to boost their collaterals in a meaningful way.
By mimicking the molecular processes that kickstart the growth of blood vessels in the heart, scientists are working on ways to encourage the growth of new collateral vessels to effectively replumb the organ.
Initially, they tried injecting the angiogenesis growth factors into the general blood supply. But clinical trials were unsuccessful. ‘ Many failed because getting an effective dose where you want it is very hard,’ says Professor Gershlick.
‘The growth factors get diluted in the circulation, so you have to give big doses to the whole body in order to treat a small area in the heart. This causes serious sideeffects.’
So various research groups are developing new treatment strategies. One technique, called gene therapy, promises to trigger the release of these growth factors directly into the heart where they are needed, avoiding unwanted sideeffects around the body and the need for invasive bypass surgery.
It uses harmless viruses to deliver a gene that, once activated, triggers the release of these angiogenesis growth factors directly into the coronary arteries.
Viruses packed with genes are prepared in a laboratory and then delivered to the heart through a wire threaded up from the leg, similar to the route taken when inserting a stent.
Once successfully implanted in a coronary artery that’s blocked, the gene switches on, producing large quantities of growth factor and stimulating the arteries to sprout new collaterals.
Gabor Rubanyi, one of the lead doctors working on this research and cofounder of a company starting a U.S. trial in 320 angina patients, has said: ‘Within the next few years, we should finally be able to offer a successful alternative to hundreds of thousands of cardiac patients who currently have no other options.’
This trial is due to start in April, comparing the new viral gene therapy, which delivers a growth factor called FGF, with a placebo.
Meanwhile, at the University of Oxford, scientists are investigating whether special stem cells in the blood can be ‘tricked’ into forming new blood vessels in the heart.
Gershlick’s research takes a different approach, and is based on more than a decade of success with socalled drugeluting stents, now used in most angioplasty procedures.
These stents are usually impregnated with drugs that prevent cells building up inside the stent and causing further obstructions.
Professor Gershlick has developed a new stent which is packed with chemicals that mimic the effects of low oxygen levels and activate the production of growth factors.
‘We just leave it in there and it acts as a reservoir in the artery,’ he explains. ‘New vessels grow out of the sides, increasing the blood supply to the area of the heart muscle beyond the blockage.’
Culled from daily mail