̽��ֱ�� of Cambridge - Ziad Mallat

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

̽��ֱ��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

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

New Heart and Lung Research Institute opens

cjb250 — Mon, 11 Jul 2022 06:31:58 +0000

A major new institute opens today, bringing together the largest concentration of scientists and clinicians in heart and lung medicine in Europe.

Could a vaccine protect us against heart attacks?

cjb250 — Thu, 20 May 2021 07:15:46 +0000

Professor Ziad Mallat and his team have been shortlisted for a £30 million grant from the British Heart Foundation. If successful, atherosclerosis – hardening of the arteries – could become a thing of the past.

̽��ֱ��Academy of Medical Sciences announces new Fellows for 2020

sc604 — Wed, 13 May 2020 01:00:00 +0000

̽��ֱ��new Fellows have been chosen for their exceptional contributions to advancing biomedical science via world-leading research discoveries, running national science communication and engagement programmes and translating scientific advances into benefits for patients and the public.

̽��ֱ��value of medical science has never been more apparent than during the current coronavirus global health crisis. From testing and vaccine development, to public health and behavioural science, to addressing the impacts of lockdown measures on mental health, biomedical and health scientists are helping to guide the UK through unprecedented challenges.

Several new Fellows have redirected their research efforts to tackle the effects of the pandemic, such as Professor Ludovic Vallier FMedSci, a stem cell expert from the ̽��ֱ�� of Cambridge, who has refocussed part of his team to study the effects of coronavirus on the liver. Professor Tamsin Ford CBE FMedSci, a Professor of Psychiatry at Cambridge, has channelled her expertise into looking at mental health impacts of the pandemic on children and young people.

Professor Sir Robert Lechler PMedSci, President of the Academy of Medical Sciences said: “This year our new Fellows announcement happens amidst a global health crisis. Never has there been a more important time to recognise and celebrate the people behind ground-breaking biomedical and health research, working harder than ever to further knowledge and protect patients and the public.

“It brings me great pleasure to congratulate the new Fellows, and see our Fellowship grow to even greater heights of evidence-based advice, leadership and expertise.”

̽��ֱ�� ̽��ֱ�� of Cambridge Fellows elected in 2020 are:

Professor Menna Clatworthy FLSW, NIHR Research Professor and Professor of Translational Immunology, ̽��ֱ�� of Cambridge and Associate Faculty, Wellcome Sanger Institute, Fellow, Pembroke College

Dr Helen Firth, Consultant Clinical Geneticist, Cambridge ̽��ֱ�� Hospitals, Honorary Faculty Member, Wellcome Sanger Institute, Bye-Fellow, Newnham College

Professor Tamsin Ford CBE, Professor of Child and Adolescent Psychiatry, ̽��ֱ�� of Cambridge, Fellow, Hughes Hall

Professor Ziad Mallat, Professor of Cardiovascular Medicine, ̽��ֱ�� of Cambridge

Dr Nitzan Rosenfeld, Senior Group Leader, Cancer Research UK Cambridge Institute, ̽��ֱ�� of Cambridge

Professor Ludovic Vallier, Professor of Regenerative Medicine, Wellcome - MRC Cambridge Stem Cell Institute, ̽��ֱ�� of Cambridge, Fellow, St Edmund’s College

̽��ֱ��new Fellows will be formally admitted to the Academy on 25 June 2020.

Six affiliates of the ̽��ֱ�� of Cambridge are among 50 world-leading UK researchers who have been elected to the prestigious Fellowship of the Academy of Medical Sciences.

Big T Images for Academy of Medical Sciences

Academy of Medical Sciences

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 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