Healing broken hearts

In the last five minutes, someone in the UK was admitted to hospital due to a heart attack.

Two-hundred and sixty people will be hospitalised today and 100,000 will be this year.

Even greater numbers will suffer from heart disease — one of the leading causes of death and premature death worldwide — and the most common trigger of a heart attack.

Strokes — which, like heart attacks, occur when the blood supply to a major organ is suddenly interrupted — cause more than 30,000 deaths in the UK each year, according to statistics from the British Heart Foundation.

And there could be life-changing impacts for those who survive, including severe disability.

But there is hope for anyone who might find themselves at risk.

Research and medical advancements over the past 50 years have significantly reduced the odds of death due to a heart attack, heart disease or stroke.

In fact, seven out of ten people who suffer a heart attack will now survive, when just 50 years ago, the odds were very much against them.

Scientists from Manchester Met hope to improve these odds even further with their work on understanding the underlying mechanisms that cause heart attacks and strokes.

They’re looking to unpick exactly what is happening inside the blood vessels, hoping that further understanding of what is causing the problem will lead to a solution

Why do hearts break?

“Heart attacks are most often caused when you get a blood clot to the artery that supplies the heart tissue with blood, and of course, when that happens, the heart becomes starved of oxygen and stops working,” explained Dr Stephen White, Reader in Cardiovascular Pathology.

Dr White described how blockages in the coronary artery can lead to blood clots and potentially trigger heart attacks. He said: “When blockages build up in your arteries — so that might be fatty deposits or cholesterol — they can burst, and this causes the blood to clot. This is known as plaque rupture.

“Another way in which a blood clot can form is when the blood vessels are damaged — so this could be by cigarette smoke or disease.

“When this happens, the inner lining of blood vessels, known as the endothelium, detaches. “The endothelium provides protection to the blood vessels, so when it falls away, the blood starts to clot, which can then trigger a heart attack. And this is known as plaque erosion.”

For the very first time, we have been able to explain what is happening inside the blood vessel when plaque erosion occurs. This has led to us being able to put forward recommendations for drug therapies that might reduce the risk of this type of heart attack. 

Dr Amanda Unsworth, Senior Lecturer in Haematology, explained why blood clots, a natural bodily process that is supposed to help us heal, form — and also why they don’t always do as they should.

She said: “The formation of a blood clot is the body’s natural approach to prevent itself from bleeding.

“When we damage a blood vessel, this leads to a tear in the vessel wall that allows blood to leak out. The body responds to this by forming a blood clot, which creates a plug that stops us from bleeding.

“Think about when you have a cut. It eventually stops bleeding on its own, and that’s because of this process. Blood clots are nature’s very own plaster.

“When a blood vessel is damaged, the endothelial cells that line the walls of the vessel very helpfully send out emergency signals.

“Platelets in our blood are our first emergency responders. They recognise these signals and start to stick down to create that platelet plug.”

But, Dr Unsworth explained in the case of heart attacks and strokes, the endothelial cells are actually sending out signals when they shouldn’t be.

“Essentially, they are accidentally setting off the fire alarm when there is no fire,” she said. “This is causing platelets to react and stick down when they don’t need to, and this can lead to a blockage.

“This can happen for many reasons, such as a response to some diseases that can damage the endothelial cells or cardiovascular risk factors like smoking. And this is what we are looking into in our research: how and why these cells start sending out these signals.

“Likewise, when there is a build-up of fatty plaques in the artery, platelets really like to stick to those plaques. Essentially, those fatty plaques are setting off the same signals that a cut would set off.

”So, while blood clots work really effectively to prevent us from bleeding out, there are certain triggers that cause them to form when they shouldn’t, and this is when things like heart attacks and strokes occur.

“But, if we can understand why this is happening, we can try to find ways of preventing it,” Dr Unsworth said.

How Manchester Met minds are healing hearts

From deciphering how different diseases are impacting blood vessel function to decoding the influence genetics has on the odds of someone suffering from a heart attack or stroke, scientists from Manchester Met are working on a range of studies that they hope will make an impact in the field of cardiovascular health.

Dr White explained his ‘voyage of discovery’ in trying to understand how one of the most common causes of heart attacks — plaque erosion — is the trigger in 30% of attacks. He said: “I’ve been working on trying to understand the mechanism behind plaque erosion for some time.

“For the very first time, we have been able to explain what is happening inside the blood vessel when plaque erosion occurs.

“This has led to us being able to put forward recommendations for drug therapies that might reduce the risk of this type of heart attack — so it’s been a real breakthrough.

“We know that smoking is a risk factor for this type of heart attack, so using the biology of cigarette smoke, we were able to analyse in the lab what was happening to the blood vessel lining.

“And although we used cigarette smoke as the trigger, we know that other factors like air pollution could easily push the same buttons of this pathway.”

Dr Sarah Jones, Reader in Thrombosis and Haemostasis, is also interested in understanding the processes behind the cause of blood clots. She said: “We want to understand how blood clot formation is regulated and how we can stop them forming in patients with cardiovascular disease. Specifically, I am looking at how the endothelial cells that line the blood vessels communicate with the platelets in the blood, which are responsible for forming blood clots.

“Ultimately, by having a greater understanding of how these cells work, we want to be able to improve endothelial function and therefore protect against blood clotting.”

Dr Jones is currently working on a project that she hopes will revolutionise how heart attack research is carried out and, ultimately, save more lives.

“We are creating new models to investigate blood clot formation using synthetic vessels lined with human endothelial cells,” she explained.

“We have also recently been awarded further funding to progress this work and develop models using human blood vessels taken from placentas.

“There are thousands of babies born every day, and with that, thousands of placentas incinerated as clinical waste.

“Now, this is a huge, valuable supply of human blood vessels that could be used in research with the purpose of helping save lives in the future.

“What we hope to do with these models is flow blood through them and analyse blood clot formation.”

The hope is that this proposed approach may address the problem that much of the research in this area is done on animals. Outside of the sensitive nature of animal testing, the added issue is the fact that an animal’s biology and blood flow are not the same as in a human.

Dr Jones explained: “With this model, we hope to gain a better understanding of blood clot regulation in humans and be able to test lots of new potential drugs to prevent heart attacks and strokes. Hopefully, we’re producing a better model that reflects human disease and, at the same time, is reducing the number of animals used in research.”

Dr Natalie Duggett, Programme Manager from the National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs), added: “In this study, Dr Jones, funded through a BHF/NC3Rs PhD Studentship, shows that by generating human-based approaches for the study of cardiovascular health we can provide valuable models to robustly replace animal use in atherothrombosis research.

“It is great to see early career researchers improving the available models in cardiovascular research.”

We have just started some new research that looks at a specific gene that has previously been identified as a risk of giving someone a heart attack, having atrial fibrillation, or having a stroke.

Dr Unsworth’s research is focused on how different diseases and conditions impact the platelets themselves, as well as how drugs for other conditions could be repurposed to help. She said: “It is known that multiple different conditions are associated with having an increased risk of heart attacks and strokes.

“For example, we know inflammatory conditions such as rheumatoid arthritis, lupus, diabetes and even people with COVID-19 all have this enhanced risk of forming blood clots.

“What I am trying to do with my research is identify molecules associated with these conditions that are driving platelets to activate and form a clot.

“We know that inflammation increases platelet production, and there’s evidence to suggest that inflammation also changes the make-up or contents of the platelets themselves. This change might make them more likely to turn themselves on and form a clot — so you can see why it’s important to understand why and how these disease conditions do this.

“If I can gain a better understanding of how platelets are produced, how they function, and what molecules control this, that’s when we can start to identify drugs — either repurposed or novel treatments — that could reduce the chances of a blood clot forming in at-risk patients.”

Genetics and identifying new risk factors for heart attacks and strokes using artificial intelligence are other areas currently being explored by the team at Manchester Met. Dr White added: “We have just started some new research that looks at a specific gene that has previously been identified as a risk of giving someone a heart attack, having atrial fibrillation, or having a stroke.

“This gene seems to be involved in all of the processes, so we are looking into the mechanism behind that, hoping to understand why it’s having such an impact.”

The research is founded on the existing knowledge that there is a link between our genetics and disease risk, which means our DNA could make us more likely to get certain conditions. And the same applies to heart attacks.

Dr White explained that he is searching for “new signatures of risk.”

“What I mean by this is, we are trying to identify new potential risks of heart attacks and strokes by taking patient records — this is patients who have suffered a heart attack previously — and analysing the risk factors,” he said.

“So, there is going to be a group of patients where it’s not a big surprise that they’ve had a heart attack because they’ll display some of the risk factors associated.

“They might be overweight, smoke or have high cholesterol, for example. These are classic risk factors for heart attacks.

“But there is going to be a group of patients who don’t have any of these, and what the study aims to do is see if there is anything novel about them — anything discrete that could have led to their heart attack.

“This will help us identify new risk factors and improve methods of identifying who is at risk, meaning they can receive targeted therapeutic intervention that could save their life.”

Heart healthy

Whether it’s a high-fat diet or high blood pressure, smoking, or a sedentary lifestyle, the causes of heart attacks vary. And although experts are working hard to find ways to prevent them, they say that there is plenty that individuals can do to reduce the risks.

Dr Stephen White explains how to keep your heart as healthy as possible for as long as possible. He said: “The biggest risk factor for having a heart attack is getting old. Now there isn’t a great deal you can do about getting older.

“Likewise, being male and other genetic factors can increase your risk.

“But, there is a lot that can be done to mitigate the risks, even if you do have age, biological sex and genetics against you.

“Having a healthy diet, getting lots of exercise, and not smoking is a good place to start.

“It doesn’t matter whether it is cancer or heart disease. Having a healthy lifestyle is going to reduce the risks of getting a range of diseases and conditions.”

The more awareness people have of the things they can do to help themselves, the better. We want to see people taking their heart and their health into their own hands as much as possible.

Dr Jones added: “It is the build-up of fatty deposits that put us at risk of cardiovascular disease, and these will develop as we age naturally — no matter how healthy we are.

“But the unhealthier the lifestyle you have, the faster this process will happen, and this leads to an acceleration of disease in the blood vessels. 

"So, we will continue with the work we are doing that will hopefully lead to more drugs and treatments being offered, better identification of people at risk, and finding new ways to prevent the formation of blood clots.

“But the more awareness people have of the things they can do to help themselves, the better. We want to see people taking their heart and their health into their own hands as much as possible.”