̽��ֱ�� of Cambridge - cardiovascular disease (CVD)

Handheld device could transform heart disease screening

sc604 — Tue, 08 Apr 2025 08:10:47 +0000

̽��ֱ��researchers, from the ̽��ֱ�� of Cambridge, developed a device that makes it easy for people with or without medical training to record heart sounds accurately. Unlike a stethoscope, the device works well even if it’s not placed precisely on the chest: its larger, flexible sensing area helps capture clearer heart sounds than traditional stethoscopes.

̽��ֱ��device can also be used over clothing, making it more comfortable for patients – especially women – during routine check-ups or community heart health screening programmes.

̽��ֱ��heart sound recordings can be saved on the device, which can then be used to detect signs of heart valve disease. ̽��ֱ��researchers are also developing a machine learning algorithm which can detect signs of valve disease automatically. ̽��ֱ��results are reported in the IEEE Journal of Biomedical and Health Informatics.

Heart valve disease (valvular heart disease or VHD) has been called the ‘next cardiac epidemic,’ with a prognosis worse than many forms of cancer. Up to 50% of patients with significant VHD remain undiagnosed, and many patients only see their doctor when the disease has advanced and they are experiencing significant complications.

In the UK, the NHS and NICE have identified early detection of heart valve disease as a key goal, both to improve quality of life for patients, and to decrease costs.

An examination with a stethoscope, or auscultation, is the way that most diagnoses of heart valve disease are made. However, just 38% of patients who present to their GP with symptoms of valve disease receive an examination with a stethoscope.

“ ̽��ֱ��symptoms of VHD can be easily confused with certain respiratory conditions, which is why so many patients don’t receive a stethoscope examination,” said Professor Anurag Agarwal from Cambridge’s Department of Engineering, who led the research. “However, the accuracy of stethoscope examination for diagnosing heart valve disease is fairly poor, and it requires a GP to conduct the examination.”

In addition, a stethoscope examination requires patients to partially undress, which is both time consuming in short GP appointments, and can be uncomfortable for patients, particularly for female patients in routine screening programmes.

̽��ֱ��‘gold standard’ for diagnosing heart valve disease is an echocardiogram, but this can only be done in a hospital and NHS waiting lists are extremely long – between six to nine months at many hospitals.

“To help get waiting lists down, and to make sure we’re diagnosing heart valve disease early enough that simple interventions can improve quality of life, we wanted to develop an alternative to a stethoscope that is easy to use as a screening tool,” said Agarwal.

Agarwal and his colleagues have developed a handheld device, about the diameter of a drinks coaster, that could be a solution. Their device can be used by any health professional to accurately record heart sounds, and can be used over clothes.

While a regular or electronic stethoscope has a single sensor, the Cambridge-developed device has six, meaning it is easier for the doctor or nurse – or even someone without any medical training – to get an accurate reading, simply because the surface area is so much bigger.

̽��ֱ��device contains materials that can transmit vibration so that it can be used over clothes, which is particularly important when conducting community screening programmes to protect patient privacy. Between each of the six sensors is a gel that absorbs vibration, so the sensors don’t interfere with each other.

̽��ֱ��researchers tested the device on healthy participants with different body shapes and sizes and recorded their heart sounds. Their next steps will be to test the device in a clinical setting on a variety of patients, against results from an echocardiogram.

In parallel with the development of the device, the researchers have developed a machine learning algorithm that can use the recorded heart sounds to detect signs of valve disease automatically. Early tests of the algorithm suggest that it outperforms GPs in detecting heart valve disease.

“If successful, this device could become an affordable and scalable solution for heart health screening, especially in areas with limited medical resources,” said Agarwal.

̽��ֱ��researchers say that the device could be a useful tool to triage patients who are waiting for an echocardiogram, so that those with signs of valve disease can be seen in a hospital sooner.

A patent has been filed on the device by Cambridge Enterprise, the ̽��ֱ��’s commercialisation arm. Anurag Agarwal is a Fellow of Emmanuel College, Cambridge.

Reference:
Andrew McDonald et al. ‘A flexible multi-sensor device enabling handheld sensing of heart sounds by untrained users.’ IEEE Journal of Biomedical and Health Informatics (2025). DOI: 10.1109/JBHI.2025.3551882

Researchers have developed a handheld device that could potentially replace stethoscopes as a tool for detecting certain types of heart disease.

This device could become an affordable and scalable solution for heart health screening, especially in areas with limited medical resources

Anurag Agarwal

Acoustics Lab

Person demonstrating use of a handheld device for heart disease screening

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

AI algorithm accurately detects heart disease in dogs

sc604 — Tue, 29 Oct 2024 02:20:22 +0000

̽��ֱ��research team, led by the ̽��ֱ�� of Cambridge, adapted an algorithm originally designed for humans and found it could automatically detect and grade heart murmurs in dogs, based on audio recordings from digital stethoscopes. In tests, the algorithm detected heart murmurs with a sensitivity of 90%, a similar accuracy to expert cardiologists.

Heart murmurs are a key indicator of mitral valve disease, the most common heart condition in adult dogs. Roughly one in 30 dogs seen by a veterinarian has a heart murmur, although the prevalence is higher in small breed dogs and older dogs.

Since mitral valve disease and other heart conditions are so common in dogs, early detection is crucial as timely medication can extend their lives. ̽��ֱ��technology developed by the Cambridge team could offer an affordable and effective screening tool for primary care veterinarians, and improve quality of life for dogs. ̽��ֱ��results are reported in the Journal of Veterinary Internal Medicine.

“Heart disease in humans is a huge health issue, but in dogs it’s an even bigger problem,” said first author Dr Andrew McDonald from Cambridge’s Department of Engineering. “Most smaller dog breeds will have heart disease when they get older, but obviously dogs can’t communicate in the same way that humans can, so it’s up to primary care vets to detect heart disease early enough so it can be treated.”

Professor Anurag Agarwal, who led the research, is a specialist in acoustics and bioengineering. “As far as we’re aware, there are no existing databases of heart sounds in dogs, which is why we started out with a database of heart sounds in humans,” he said. “Mammalian hearts are fairly similar, and when things go wrong, they tend to go wrong in similar ways.”

̽��ֱ��researchers started with a database of heart sounds from about 1000 human patients and developed a machine learning algorithm to replicate whether a heart murmur had been detected by a cardiologist. They then adapted the algorithm so it could be used with heart sounds from dogs.

̽��ֱ��researchers gathered data from almost 800 dogs who were undergoing routine heart examination at four veterinary specialist centres in the UK. All dogs received a full physical examination and heart scan (echocardiogram) by a cardiologist to grade any heart murmurs and identify cardiac disease, and heart sounds were recorded using an electronic stethoscope. By an order of magnitude, this is the largest dataset of dog heart sounds ever created.

“Mitral valve disease mainly affects smaller dogs, but to test and improve our algorithm, we wanted to get data from dogs of all shapes, sizes and ages,” said co-author Professor Jose Novo Matos from Cambridge’s Department of Veterinary Medicine, a specialist in small animal cardiology. “ ̽��ֱ��more data we have to train it, the more useful our algorithm will be, both for vets and for dog owners.”

̽��ֱ��researchers fine-tuned the algorithm so it could both detect and grade heart murmurs based on the audio recordings, and differentiate between murmurs associated with mild disease and those reflecting advanced heart disease that required further treatment.

“Grading a heart murmur and determining whether the heart disease needs treatment requires a lot of experience, referral to a veterinary cardiologist, and expensive specialised heart scans,” said Novo Matos. “We want to empower general practitioners to detect heart disease and assess its severity to help owners make the best decisions for their dogs.”

Analysis of the algorithm’s performance found it agreed with the cardiologist’s assessment in over half of cases, and in 90% of cases, it was within a single grade of the cardiologist’s assessment. ̽��ֱ��researchers say this is a promising result, as it is common for there to be significant variability in how different vets grade heart murmurs.

“ ̽��ֱ��grade of heart murmur is a useful differentiator for determining next steps and treatments, and we’ve automated that process,” said McDonald. “For vets and nurses without as much stethoscope skill, and even those who are incredibly skilled with a stethoscope, we believe this algorithm could be a highly valuable tool.”

In humans with valve disease, the only treatment is surgery, but for dogs, effective medication is available. “Knowing when to medicate is so important, in order to give dogs the best quality of life possible for as long as possible,” said Agarwal. “We want to empower vets to help make those decisions.”

“So many people talk about AI as a threat to jobs, but for me, I see it as a tool that will make me a better cardiologist,” said Novo Matos. “We can’t perform heart scans on every dog in this country – we just don’t have enough time or specialists to screen every dog with a murmur. But tools like these could help vets and owners, so we can quickly identify those dogs who are most in need of treatment.”

̽��ֱ��research was supported in part by the Kennel Club Charitable Trust, the Medical Research Council, and Emmanuel College Cambridge.

Reference:
Andrew McDonald et al. ‘A machine learning algorithm to grade canine heart murmurs and stage preclinical myxomatous mitral valve disease.’ Journal of Veterinary Internal Medicine (2024). DOI: 10.1111/jvim.17224

Researchers have developed a machine learning algorithm to accurately detect heart murmurs in dogs, one of the main indicators of cardiac disease, which affects a large proportion of some smaller breeds such as King Charles Spaniels.

Jacqueline Garget

Huxley, a healthy volunteer Havanese, undergoes a physical examination at the Queen's Veterinary School Hospital, Cambridge.

Yes

High cholesterol levels at a young age significant risk factor for atherosclerosis

cjb250 — Wed, 04 Sep 2024 15:00:18 +0000

̽��ֱ��research also suggests that people who are taking lipid-lowering drugs such as statins to lower their cholesterol levels should remain on them, even if their cholesterol levels have fallen, as stopping treatment could increase their risk of atherosclerosis.

Atherosclerosis is one of the major causes of heart and circulatory disease. It involves the hardening and narrowing of the vessels that carry blood to and from the heart. It is caused by the build-up of abnormal material called plaques – collections of fat, cholesterol, calcium and other substances circulating in the blood.

Atherosclerosis is largely considered a disease of the elderly and so most screening, prevention and intervention programmes primarily target those with high cholesterol levels, generally after the age of 50.

But in a study published today in Nature, a team led by scientists at the ̽��ֱ�� of Cambridge shows that high cholesterol levels at a younger age – particularly if those levels fluctuate – can be even more damaging than high cholesterol levels that only begin in later life.

To study the mechanisms that underlie atherosclerosis, scientists often use animal modes, such as mice. ̽��ֱ��mice will typically be fed a high fat diet for several weeks as adults to see how this leads to the build up of the plaques characteristic of the condition.

Professor Ziad Mallat and colleagues at the Victor Phillip Dahdaleh Heart and Lung Research Institute at the ̽��ֱ�� of Cambridge decided to explore a different approach – to see whether giving mice the same amount of high fat food but spread over their lifetime changed their atherosclerosis risk.

“When I asked my group and a number of people who are experts in atherosclerosis, no one could tell me what the result would be,” said Professor Mallat, a British Heart Foundation (BHF) Professor of Cardiovascular Medicine.

“Some people thought it would make no difference, others thought it would change the risk. In fact, what we found was that an intermittent high fat diet starting while the mice were still young – one week on, a few weeks off, another week on, and so on – was the worst option in terms of atherosclerosis risk.”

Armed with this information, his team turned to the Cardiovascular Risk in Young Finns Study, one of the largest follow-up studies into cardiovascular risk from childhood to adulthood. Participants recruited in the 1980s returned for follow-up over the subsequent decades, and more than 2,000 of them had received ultrasound scans of their carotid arteries when they were aged around 30 years and again at around 50 years.

Analysing the data, the team found that those participants who had been exposed to high cholesterol levels as children tended to have the biggest build of plaques, confirming the findings in mice.

“What this means is that we shouldn’t leave it until later in life before we start to look at our cholesterol levels,” Professor Mallat said. “Atherosclerosis can potentially be prevented by lowering cholesterol levels, but we clearly need to start thinking about this much earlier on in life than we previously thought.”

̽��ֱ��mouse studies showed that fluctuating levels of cholesterol appeared to cause the most damage. Professor Mallat says this could explain why some people who are on statins but do not take them regularly remain at an increased risk of heart attack.

“If you stop and start your statin treatment, your body is being exposed to a yo-yo of cholesterol, which it doesn’t like, and it seems this interferes with your body’s ability to prevent the build-up of plaques,” he added.

̽��ֱ��reason why this is so damaging may come down to the effect that cholesterol has on specific types of immune cells known as ‘resident arterial macrophages’. These reside in your arteries, helping them to clear damaged cells and fatty molecules known as lipids, which include cholesterol, and stopping the build-up of plaques.

When the team examined these macrophages in their mouse models, they found that high cholesterol levels – and in particular, fluctuating cholesterol levels – changed them physically and altered the activity of their genes. This meant that the cells were no longer protective, but were instead detrimental, accelerating atherosclerosis.

̽��ֱ��research was funded by the British Heart Foundation.

Reference
Takaoka, M et al. Early intermittent hyperlipidaemia alters tissue macrophages to boost atherosclerosis. Nature; 4 Sept 2024; DOI: 10.1038/s41586-024-07993-x

Our risk of developing atherosclerosis – ‘furring’ of the arteries – can begin much earlier in life than was previously thought, highlighting the need to keep cholesterol levels low even when we are young, new research has discovered.

Atherosclerosis can potentially be prevented by lowering cholesterol levels, but we clearly need to start thinking about this much earlier on in life

Ziad Mallat

SolStock (Getty Images)

Teenagers eating pizza by the river

Yes

Anti-inflammatory drug could reduce future heart attack risk

Anonymous — Mon, 02 Sep 2024 10:52:31 +0000

A cancer drug that unlocks the anti-inflammatory power of the immune system could help to reduce the risk of future heart attacks, according to research part-funded by the British Heart Foundation. By repurposing an existing drug, researchers hope it could soon become part of routine treatment for patients after a heart attack.

̽��ֱ��findings will be presented at the European Society of Cardiology Congress in London by Dr Rouchelle Sriranjan, NIHR Clinical Lecturer in Cardiology at the ̽��ֱ�� of Cambridge.

High levels of inflammation in blood vessels are linked to an increased risk of heart disease and heart attacks. After a heart attack, the body’s immune response can aggravate existing inflammation, causing more harm and increasing risk even further. However, NICE guidelines don’t currently recommend the use of any anti-inflammatory drugs to reduce future risk.

Now, a team of researchers, led by Dr Joseph Cheriyan from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, have found that low doses of an anti-inflammatory drug called aldesleukin, injected under the skin of patients after a heart attack, significantly reduces inflammation in arteries.

̽��ֱ��researchers are currently following up patients to investigate the longer-term impact of this fall in inflammation. To date, in the two and a half years after their treatment, there have been no major adverse cardiac events in the group that received aldesleukin, compared to seven in the group that received the placebo.

Professor Ziad Mallat, BHF Professor of Cardiovascular Medicine at the ̽��ֱ�� of Cambridge who developed the trial, said: “We associate inflammation with healing – an inbuilt response that protects us from infection and injury. But it’s now clear that inflammation is a culprit in many cardiovascular conditions.

“Early signs from our ongoing trial suggest that people treated with aldesleukin may have better long-term outcomes, including fewer heart attacks. If these findings are repeated in a larger trial, we’re hopeful that aldesleukin could become part of routine care after a heart attack within five to 10 years.”

Aldesleukin is already used to treat kidney cancer, as high doses stimulate the immune system to attack cancer cells. ̽��ֱ��Cambridge team previously found that doses one thousand times lower than those used in cancer treatment increased the number of regulatory T cells – a type of anti-inflammatory white blood cell – in patients’ blood compared to a placebo.

In the current trial at Addenbrooke's and Royal Papworth hospitals in Cambridge, 60 patients admitted to hospital with a heart attack or unstable angina received either low dose aldesleukin or placebo. Patients received an injection once a day for the first five days, then once per week over the next seven weeks. Neither the participants nor their doctors knew whether they had received the drug or placebo.

At the end of treatment, Positron Emission Tomography (PET) scans showed that inflammation in the artery involved in patients’ heart attack or angina was significantly lower in the group treated with aldesleukin, compared to those who received the placebo.

̽��ֱ��anti-inflammatory effect of aldesleukin appeared even more striking in the most inflamed arteries, leading to a larger reduction in inflammation levels in these vessels and a bigger difference between the two groups by the end of the study.

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation and consultant cardiologist said: “Thanks to research, we have an array of effective treatments to help people avoid heart attacks and strokes and save lives. But, even after successful heart attack treatment, unwanted inflammation in the coronary arteries can remain, which can lead to life-threatening complications.

“A treatment to reduce inflammation after a heart attack could be a game-changer. It would help doctors to interrupt the dangerous feedback loop that exacerbates inflammation and drives up risk. This research is an important step towards that treatment becoming a reality.”

̽��ֱ��study was predominantly funded by the Medical Research Council, with significant support from the BHF and National Institute for Health and Care Research Cambridge Biomedical Research Centre (NIHR-BRC).

Originally published by the British Heart Foundation.

Repurposed cancer drug helps to calm inflammation in arteries.

Sebastian Kaulitzki/Science Photo Library via Getty Images

Illustration of human heart

Yes

Incidence of heart attacks and strokes was lower after COVID-19 vaccination

cjb250 — Wed, 31 Jul 2024 09:00:37 +0000

̽��ֱ��study, published today in Nature Communications, showed that the incidence of arterial thromboses, such as heart attacks and strokes, was up to 10% lower in the 13 to 24 weeks after the first dose of a COVID-19 vaccine. Following a second dose, the incidence was up to 27% lower after receiving the AstraZeneca vaccine and up to 20% lower after the Pfizer/Biotech vaccine.

̽��ֱ��incidence of common venous thrombotic events – mainly pulmonary embolism and lower limb deep venous thrombosis – followed a similar pattern.

Research led by the Universities of Cambridge, Bristol and Edinburgh and enabled by the British Heart Foundation (BHF) Data Science Centre at Health Data Research UK analysed de-identified health records from 46 million adults in England between 8 December 2020 and 23 January 2022. Data scientists compared the incidence of cardiovascular diseases after vaccination with the incidence before or without vaccination, during the first two years of the vaccination programme.

Co-first author Dr Samantha Ip, Research Associate at the Department of Public Health and Primary Care, ̽��ֱ�� of Cambridge, said: “We studied COVID-19 vaccines and cardiovascular disease in nearly 46 million adults in England and found a similar or lower incidence of common cardiovascular diseases, such as heart attacks and strokes, following each vaccination than before or without vaccination. This research further supports the large body of evidence on the safety of the COVID-19 vaccination programme, which has been shown to provide protection against severe COVID-19 and saved millions of lives worldwide.”

Previous research found that the incidence of rare cardiovascular complications is higher after some COVID-19 vaccines. For example, incidence of myocarditis and pericarditis have been reported following mRNA-based vaccines such as the Pfizer/Biotech vaccine, and vaccine-induced thrombotic thrombocytopenia following adenovirus-based vaccines such as the AstraZeneca vaccine. This study supports these findings, but importantly it did not identify new adverse cardiovascular conditions associated with COVID-19 vaccination and offers further reassurance that the benefits of vaccination outweigh the risk.

Incidence of cardiovascular disease is higher after COVID-19, especially in severe cases. This may explain why incidence of heart attacks and strokes is lower in vaccinated people compared with unvaccinated people, but further explanations are beyond the scope of this study.

Professor William Whiteley, Associate Director at the BHF Data Science Centre and Professor of Neurology and Epidemiology at the ̽��ֱ�� of Edinburgh, said: “ ̽��ֱ��COVID-19 vaccination programme rollout began strongly in the UK, with over 90% of the population over the age of 12 vaccinated with at least one dose by January 2022.

“This England-wide study offers patients reassurance of the cardiovascular safety of first, second and booster doses of COVID-19 vaccines. It demonstrates that the benefits of second and booster doses, with fewer common cardiovascular events include heart attacks and strokes after vaccination, outweigh the very rare cardiovascular complications.”

̽��ֱ��research team used de-identified linked data from GP practices, hospital admissions and death records, analysed in a secure data environment provided by NHS England.

Co-last author Dr Venexia Walker, Research Fellow at the ̽��ֱ�� of Bristol, said: “Given the critical role of COVID-19 vaccines in protecting people from COVID-19, it is important we continue to study the benefits and risks associated with them. ̽��ֱ��availability of population-wide data has allowed us to study different combinations of COVID-19 vaccines and to consider rare cardiovascular complications. This would not have been possible without the very large data that we are privileged to access and our close cross-institution collaborations.”

Reference
Ip, S et al. Cohort study of cardiovascular safety of different COVID-19 vaccination doses among 46 million adults in England. Nat Comms; 31 Jul 2024; DOI: 10.1038/s41467-024-49634-x

Adapted from a press release from Health Data Research UK

̽��ֱ��incidence of heart attacks and strokes was lower after COVID-19 vaccination than before or without vaccination, according to a new study involving nearly the whole adult population of England.

This research further supports the large body of evidence on the effectiveness of the COVID-19 vaccination programme, which has saved millions of lives worldwide

Samantha Ip

Paul_McManus

Vial of the AstraZeneca COVID-19 vaccine

Yes

Licence type:

Public Domain

Cambridge research receives £5 million boost for ‘world-leading’ cardiovascular research

cjb250 — Tue, 28 May 2024 11:10:58 +0000

̽��ֱ��funding will support the university to cultivate a world-class research environment that encourages collaboration, inclusion and innovation, and where visionary scientists can drive lifesaving breakthroughs.

Professor Martin Bennett, BHF Professor of Cardiovascular Sciences at the ̽��ֱ�� of Cambridge, said: “This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes identifying new targets and treatments for vascular disease and heart failure, new ways to reduce the consequences of diabetes and obesity, and how we can get our research used to treat patients.”

̽��ֱ��Cambridge award is part of a £35 million boost to UK cardiovascular disease research from the British Heart Foundation. It comes from the charity’s highly competitive Research Excellence Awards funding scheme. ̽��ֱ��£5 million award to the ̽��ֱ�� of Cambridge will support researchers to:

Combine their expertise to work on cardiovascular diseases and in populations with high unmet need.
Identify new markers and disease targets for a wide range of cardiovascular diseases, and test new drugs in clinical trials.
Develop new ways to diagnose cardiovascular disease and harness the power of artificial intelligence from imaging and health records to identify people at highest risk.
Generate user-friendly risk communication and management tools to improve the prevention and management of cardiovascular disease.

Professor Bryan Williams, Chief Scientific and Medical Officer at the British Heart Foundation, said: “We’re delighted to continue to support research at the ̽��ֱ�� of Cambridge addressing the biggest challenges in cardiovascular disease. This funding recognises the incredible research happening at Cambridge and will help to further its reputation as a global leader in the field.

“With generous donations from our supporters, this funding will attract the brightest talent, power cutting-edge science, and unlock lifesaving discoveries that can turn the tide on the devastation caused by heart and circulatory diseases.”

Research Excellence Awards offer greater flexibility than traditional research funding, allowing scientists to quickly launch ambitious projects that can act as a springboard for larger, transformative funding applications.

̽��ֱ��funding also aims to break down the silos that have traditionally existed in research, encouraging collaboration between experts from diverse fields. From clinicians to data scientists, biologists to engineers, the funding will support universities to attract the brightest minds, nurture new talent and foster collaboration to answer the biggest questions in heart and circulatory disease research.

̽��ֱ�� ̽��ֱ�� of Cambridge has previously been awarded £9 million funding through the BHF’s Research Excellence Awards scheme. This funding has supported research that will lay the foundations for future breakthroughs, including:

Research showing that low doses of a cancer drug could improve recovery after a heart attack. ̽��ֱ��drug boosts activity of anti-inflammatory immune cells that can cause harmful inflammation in blood vessels supplying the heart. It’s currently being tested in clinical trials to see if it benefits patients.
A new risk calculator to enable doctors across the UK and Europe predict who is at risk of having a heart attack or stroke in the next 10 years with greater accuracy. ̽��ֱ��calculator has been adopted by the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice.
Developing imaging and artificial intelligence tools to improve diagnosis of heart and vascular disease by enhancing analysis of scans for disease activity and high-risk fatty plaques. These tools can be rapidly implemented to support diagnosis, treatment and prevention.
A study investigating whether an epilepsy medication could help to prevent strokes in people with a common gene variant. ̽��ֱ��change in the gene HDAC9 can cause it to become ‘overactive’ and increase stroke risk. ̽��ֱ��epilepsy medication sodium valproate blocks the HDAC9 activity, so could reduce stroke risk in people with the variant.
Discovery of rare and common changes in the genetic code that influences proteins and small molecules in the blood, helping us understand the development of cardiovascular diseases and identify novel drug targets.

Adapted from a press release by BHF

̽��ֱ�� ̽��ֱ�� of Cambridge has received £5 million funding from the British Heart Foundation (BHF) to support its world-class cardiovascular disease research over the next five years, the charity has announced.

This is a fantastic achievement from the whole Cambridge team. This award will support our multiple research programmes.

Martin Bennett

Lloyd Mann

Professor Martin Bennett standing outside the Victor Phillip Dahdaleh Heart and Lung Research Institute

Yes

Lab-grown ‘small blood vessels’ point to potential treatment for major cause of stroke and vascular dementia

cjb250 — Thu, 16 Nov 2023 16:00:19 +0000

̽��ֱ��study, published today in Stem Cell Reports, also identifies a drug target to ‘plug’ these leaks and prevent so-called small vessel disease in the brain.

Cerebral small vessel disease (SVD) is a leading cause of age-related cognitive decline and contributes to almost half (45%) of dementia cases worldwide. It is also responsible for one in five (20%) ischemic strokes, the most common type of stroke, where a blood clot prevents the flow of blood and oxygen to the brain.

̽��ֱ��majority of cases of SVD are associated with conditions such as hypertension and type 2 diabetes, and tend to affect people in their middle age. However, there are some rare, inherited forms of the disease that can strike people at a younger age, often in their mid-thirties. Both the inherited and ‘spontaneous’ forms of the disease share similar characteristics.

Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute, ̽��ֱ�� of Cambridge, used cells taken from skin biopsies of patients with one of these rare forms of SVD, which is caused by a mutation in a gene called COL4.

By reprogramming the skin cells, they were able to create induced pluripotent stem cells – cells that have the capacity to develop into almost any type of cell within the body. ̽��ֱ��team then used these stem cells to generate cells of the brain blood vessels and create a model of the disease that mimics the defects seen in patients’ brain vessels.

Dr Alessandra Granata from the Department of Clinical Neurosciences at Cambridge, who led the study, said: “Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease. Most of what we know about the underlying causes tends to come from animal studies, but they are limited in what they can tell us.

“That’s why we turned to stem cells to generate cells of the brain blood vessels and create a disease model ‘in a dish’ that mimics what we see in patients.”

Our blood vessels are built around a type of scaffolding known as an extracellular matrix, a net-like structure that lines and supports the small blood vessels in the brain. ̽��ֱ��COL4 gene is important for the health of this matrix.

In their disease model, the team found that the extracellular matrix is disrupted, particularly at its so-called ‘tight junctions’, which ‘zip’ cells together. This leads to the small blood vessels becoming leaky – a key characteristic seen in SVD, where blood leaks out of the vessels and into the brain.

̽��ֱ��researchers identified a class of molecules called metalloproteinases (MMPs) that play a key role in this damage. Ordinarily, MMPs are important for maintaining the extracellular matrix, but if too many of them are produced, they can damage the structure – similar to how in ̽��ֱ��Sorcerer’s Apprentice, a single broom can help mop the floor, but too many wreak havoc.

When the team treated the blood vessels with drugs that inhibit MMPs – an antibiotic and anti-cancer drug – they found that these reversed the damage and stopped the leakage.

Dr Granata added: “These particular drugs come with potentially significant side effects so wouldn’t in themselves be viable to treat small vessel disease. But they show that in theory, targeting MMPs could stop the disease. Our model could be scaled up relatively easily to test the viability of future potential drugs.”

̽��ֱ��study was funded by the Stroke Association, British Heart Foundation and Alzheimer’s Society, with support from the NIHR Cambridge Biomedical Research Centre and the European Union’s Horizon 2020 Programme.

Reference
Al-Thani, M, Goodwin-Trotman, M. A novel human 1 iPSC model of COL4A1/A2 small vessel disease unveils a key pathogenic role of matrix metalloproteinases. Stem Cell Reports; 16 Nov 2023; DOI: https://doi.org/10.1016/j.stemcr.2023.10.014

Cambridge scientists have grown small blood vessel-like models in the lab and used them to show how damage to the scaffolding that supports these vessels can cause them to leak, leading to conditions such as vascular dementia and stroke.

Despite the number of people affected worldwide by small vessel disease, we have little in the way of treatments because we don’t fully understand what damages the blood vessels and causes the disease

Alessandra Granata

Alessandra Granata/ ̽��ֱ�� of Cambridge

Disease mural cells stained for calponin (mural cells marker, green), collagen IV (magenta) and DAPI (nuclei, blue)

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

Licence type:

Attribution

Cancer drug could hold hope for treating inflammatory diseases including gout and heart diseases

cjb250 — Wed, 01 Nov 2023 08:00:30 +0000

In a study published on 1 November in the Journal of Clinical Investigation, the researchers have identified a molecule that plays a key role in triggering inflammation in response to materials in the body seen as potentially harmful.

We are born with a defence system known as innate immunity, which acts as the first line of defence against harmful materials in the body. Some of these materials will come from outside, such as bacterial or viral infections, while others can be produced within the body.

Innate immunity triggers an inflammatory response, which aims to attack and destroy the perceived threat. But sometimes, this response can become overactive and can itself cause harm to the body.

One such example of this is gout, which occurs when urate crystals build up in joints, causing excessive inflammation, leading to intense pain. Another example is heart attack, where dead cell build up in the damaged heart – the body sees itself as being under attack and an overly-aggressive immune system fights back, causing collateral damage to the heart.

Several of these conditions are characterised by overactivation of a component of the innate immune response known as an inflammasome – specifically, the inflammasome NLRP3. Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute at Cambridge have found a molecule that helps NLRP3 respond.

This molecule is known as PLK1. It is involved in a number of processes within the body, including helping organise tiny components of our cells known as microtubules cytoskeletons. These behave like train tracks inside of the cell, allowing important materials to be transported from one part of the cell to another.

Dr Xuan Li from the Department of Medicine at the ̽��ֱ�� of Cambridge, the study’s senior author, said: “If we can get in the way of the microtubules as they try to organise themselves, then we can in effect slow down the inflammatory response, preventing it from causing collateral damage to the body. We believe this could be important in preventing a number of common diseases that can cause pain and disability and in some cases can lead to life-threatening complications.”

But PLK1 also plays another important role in the body – and this may hold the key to developing new treatments for inflammatory diseases.

For some time now, scientists have known that PLK1 is involved in cell division, or mitosis, a process which, when it goes awry, can lead to runaway cell division and the development of tumours. This has led pharmaceutical companies to test drugs that inhibit its activity as potential treatments for cancer. At least one of these drugs is in phase three clinical trials – the final stages of testing how effective a drug is before it can be granted approval.

When the Cambridge scientists treated mice that had developed inflammatory diseases with a PLK1 inhibitor, they showed that it prevented the runaway inflammatory response – and at a much lower dose than would be required for cancer treatment. In other words, inhibiting the molecule ‘calmed down’ NLRP3 in non-dividing cells, preventing the overly aggressive inflammatory response seen in these conditions.

̽��ֱ��researchers are currently planning to test its use against inflammatory diseases in clinical trials.

“These drugs have already been through safety trials for cancer – and at higher doses than we think we would need – so we’re optimistic that we can minimise delays in meeting clinical and regulatory milestones,” added Dr Li.

“If we find that the drug is effective for these conditions, we could potentially see new treatments for gout and inflammatory heart diseases – as well as a number of other inflammatory conditions – in the not-too-distant future.”

̽��ֱ��research was funded by the British Heart Foundation. Professor James Leiper, Associate Medical Director at the British Heart Foundation said: “This innovative research has uncovered a potential new treatment approach for inflammatory heart diseases such as heart failure and cardiomyopathy. It’s promising that drugs targeting PLK1 – that work by dampening down the inflammatory response – have already been proven safe and effective in cancer trials, potentially helping accelerate the drug discovery process.

“We hope that this research will open the door for new ways to treat people with heart diseases caused by overactive and aggressive immune responses, and look forward to more research to uncover how this drug could be could be repurposed.”

Reference
Baldrighi, M et al. PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models. JCI; 1 Nov 2023; DOI: 10.1172/JCI162129

A cancer drug currently in the final stages of clinical trials could offer hope for the treatment of a wide range of inflammatory diseases, including gout, heart failure, cardiomyopathy, and atrial fibrillation, say scientists at the ̽��ֱ�� of Cambridge.

We believe [our findings] could be important in preventing a number of common diseases that can cause pain and disability and in some cases can lead to life-threatening complications

Xuan Li

kazuma seki (Getty Images)

̽��ֱ��feet of a man suffering from gout - stock photo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes