William Harvey Research Institute

London, United Kingdom

William Harvey Research Institute

London, United Kingdom
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News Article | May 26, 2017
Site: www.sciencedaily.com

Diesel pollution is linked with heart damage, according to research presented today at EuroCMR 2017.1 "There is strong evidence that particulate matter (PM) emitted mainly from diesel road vehicles is associated with increased risk of heart attack, heart failure, and death," said lead author Dr Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. "This appears to be driven by an inflammatory response -- inhalation of fine particulate matter (PM2.5) causes localised inflammation of the lungs followed by a more systemic inflammation affecting the whole body. " The current study examined whether PM2.5 may damage the heart directly. The study included 4 255 participants from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was conducted to measure left ventricular volume (structure) and left ventricular ejection fraction (function). Annual average exposure to PM2.5 was calculated based on participants' home address. The association between PM2.5 exposure and heart structure and function was estimated using multivariable linear regression, a form of statistical modelling which adjusts for potential factors that could influence the relationship such as age, gender, diabetes and blood pressure. Participants were 62 years old on average and 47% were men. The annual average PM2.5 level was 10 µg/m3. The investigators found linear relationships between ambient PM2.5 level and heart structure and function. Every 5 µg/m3 increase in exposure was associated with a 4-8% increase in left ventricular volume and a 2% decrease in left ventricular ejection fraction. Dr Aung said: "We found that as PM2.5 exposure rises, the larger the heart gets and the worse it performs. Both of these measures are associated with increased morbidity and mortality from heart disease." The researchers also looked for potential factors that could modify the relationship. They found that people with degree-level education were less prone to having a larger heart and had a smaller reduction in ejection fraction when exposed to PM2.5 than people with a lower level of education. Dr Aung said: "People who were highly educated were less likely to have harmful effects on the heart from pollution. This could be due to a number of factors including better housing and workplace conditions, which reduce pollution exposure. Educated people may also be more aware of their health, have healthier lifestyles, and have better access to healthcare." Regarding how pollution might have these negative effects on the heart, Dr Aung said PM2.5 causes systemic inflammation, vasoconstriction and raised blood pressure. The combination of these factors can increase the pressure in the heart, which enlarges to cope with the overload. The heart chamber enlargement reduces the contractile efficiency leading to reduction in ejection fraction. Dr Aung said: "We found that the average exposure to PM2.5 in the UK is about 10 µg/m3 in our study. This is way below the European target of less than 25 µg/m3 and yet we are still seeing these harmful effects. This suggests that the current target level is not safe and should be lowered." He continued: "Our results suggest that PM2.5 is linked with negative changes in the heart structure and function that are associated with poor outcomes. Reducing PM2.5 emission should be an urgent public health priority and the worst offenders such as diesel vehicles should be addressed with policy measures." In terms of what individuals can do to decrease their risk, Dr Aung said: "Avoid times and places where there is a high level of pollution. If you want to cycle into work and there is heavy traffic around that time then try to find a quieter route. Walk on the part of the pavement furthest from cars to reduce the amount of pollution you breathe in. Those with cardiorespiratory diseases should limit the time spent outdoors during highly polluted periods such as rush hours."


News Article | May 29, 2017
Site: www.sciencedaily.com

Statins are associated with improved heart structure and function, according to research presented at EuroCMR 2017.1 The benefits were above and beyond the cholesterol lowering effect of statins. "Statins are primarily used to lower cholesterol," said lead author Dr Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. "They are highly effective in preventing cardiovascular events in patients who have had a heart attack or are at risk of heart disease." He continued: "Statins have other beneficial, non-cholesterol lowering, effects. They can improve the function of the blood vessels, reduce inflammation, and stabilise fatty plaques in the blood vessels. Studies in mice and small studies in humans have shown that statins also reduce the thickness of heart muscle but this needed to be confirmed in a larger study." This study investigated the association between statins and heart structure and function. The study included 4,622 people without cardiovascular disease from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was used to measure left and right ventricular volumes and left ventricular mass. Information on statin use was obtained from medical records and a self-reporting questionnaire. The relationship between statin use and heart structure and function was assessed using a statistical technique called multiple regression which adjusts for potential confounders that can have an effect on the heart such as ethnicity, gender, age, and body mass index (BMI). Nearly 17% of participants were taking statins. Those taking statins were older, had higher BMI and blood pressure, and were more likely to have diabetes and hypertension. "This was not surprising because we prescribe statins to patients at high risk of heart disease and these are all known risk factors," said Dr Aung. Patients taking statins had a 2.4% lower left ventricular mass and lower left and right ventricular volumes. Dr Aung said: "People using statins were less likely to have a thickened heart muscle (left ventricular hypertrophy) and less likely to have a large heart chamber. Having a thick, large heart is a strong predictor of future heart attack, heart failure or stroke and taking statins appears to reverse the negative changes in the heart which, in turn, could lower the risk of adverse outcomes." "It is important to note that in our study, the people taking statins were at higher risk of having heart problems than those not using statins yet they still had positive heart remodelling compared to the healthier control group," added Dr Aung. In terms of how statins might reduce the thickness and volume of the heart, Dr Aung said several studies have demonstrated that statins reduce oxidative stress and dampen the production of growth factors which stimulate cell growth. Statins also increase the production of nitric oxide by the cells lining the blood vessels, leading to vasodilatation, improved blood flow, lower blood pressure, and lower stress on the heart, which is less likely to become hypertrophied. The findings raise the issue of extending statin prescriptions to anyone above the age of 40, but Dr Aung said that was probably not the way to go. "There are clear guidelines on who should receive statins," he said. "There is debate about whether we should lower the bar and the question is when do you stop. What we found is that for patients already taking statins, there are beneficial effects beyond cholesterol lowering and that's a good thing. But instead of a blanket prescription we need to identify people most likely to benefit -- i.e. personalised medicine." Dr Aung said: "A dual approach should be considered to identify people who will benefit most from statins. That means looking at not only clinical risk factors such as smoking and high blood pressure, but also genetic (hereditary) factors which can predict individuals' response to statins. This is an area of growing interest and one that we are also investigating in our lab with our collaborators."


News Article | May 26, 2017
Site: www.eurekalert.org

Prague, Czech Republic - 26 May 2017: Statins are associated with improved heart structure and function, according to research presented today at EuroCMR 2017.1 The benefits were above and beyond the cholesterol lowering effect of statins. "Statins are primarily used to lower cholesterol," said lead author Dr Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. "They are highly effective in preventing cardiovascular events in patients who have had a heart attack or are at risk of heart disease." He continued: "Statins have other beneficial, non-cholesterol lowering, effects. They can improve the function of the blood vessels, reduce inflammation, and stabilise fatty plaques in the blood vessels. Studies in mice and small studies in humans have shown that statins also reduce the thickness of heart muscle but this needed to be confirmed in a larger study." This study investigated the association between statins and heart structure and function. The study included 4,622 people without cardiovascular disease from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was used to measure left and right ventricular volumes and left ventricular mass. Information on statin use was obtained from medical records and a self-reporting questionnaire. The relationship between statin use and heart structure and function was assessed using a statistical technique called multiple regression which adjusts for potential confounders that can have an effect on the heart such as ethnicity, gender, age, and body mass index (BMI). Nearly 17% of participants were taking statins. Those taking statins were older, had higher BMI and blood pressure, and were more likely to have diabetes and hypertension. "This was not surprising because we prescribe statins to patients at high risk of heart disease and these are all known risk factors," said Dr Aung. Patients taking statins had a 2.4% lower left ventricular mass and lower left and right ventricular volumes. Dr Aung said: "People using statins were less likely to have a thickened heart muscle (left ventricular hypertrophy) and less likely to have a large heart chamber. Having a thick, large heart is a strong predictor of future heart attack, heart failure or stroke and taking statins appears to reverse the negative changes in the heart which, in turn, could lower the risk of adverse outcomes." "It is important to note that in our study, the people taking statins were at higher risk of having heart problems than those not using statins yet they still had positive heart remodelling compared to the healthier control group," added Dr Aung. In terms of how statins might reduce the thickness and volume of the heart, Dr Aung said several studies have demonstrated that statins reduce oxidative stress and dampen the production of growth factors which stimulate cell growth. Statins also increase the production of nitric oxide by the cells lining the blood vessels, leading to vasodilatation, improved blood flow, lower blood pressure, and lower stress on the heart, which is less likely to become hypertrophied. The findings raise the issue of extending statin prescriptions to anyone above the age of 40, but Dr Aung said that was probably not the way to go. "There are clear guidelines on who should receive statins," he said. "There is debate about whether we should lower the bar and the question is when do you stop. What we found is that for patients already taking statins, there are beneficial effects beyond cholesterol lowering and that's a good thing. But instead of a blanket prescription we need to identify people most likely to benefit - i.e. personalised medicine." Dr Aung said: "A dual approach should be considered to identify people who will benefit most from statins. That means looking at not only clinical risk factors such as smoking and high blood pressure, but also genetic (hereditary) factors which can predict individuals' response to statins. This is an area of growing interest and one that we are also investigating in our lab with our collaborators."


News Article | May 26, 2017
Site: www.eurekalert.org

PM2.5 associated with harmful changes to heart structure and function; higher education protective against the damage Prague, Czech Republic - 26 May 2017: Diesel pollution is linked with heart damage, according to research presented today at EuroCMR 2017.1 "There is strong evidence that particulate matter (PM) emitted mainly from diesel road vehicles is associated with increased risk of heart attack, heart failure, and death," said lead author Dr Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. "This appears to be driven by an inflammatory response - inhalation of fine particulate matter (PM2.5) causes localised inflammation of the lungs followed by a more systemic inflammation affecting the whole body. " The current study examined whether PM2.5 may damage the heart directly. The study included 4 255 participants from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was conducted to measure left ventricular volume (structure) and left ventricular ejection fraction (function). Annual average exposure to PM2.5 was calculated based on participants' home address. The association between PM2.5 exposure and heart structure and function was estimated using multivariable linear regression, a form of statistical modelling which adjusts for potential factors that could influence the relationship such as age, gender, diabetes and blood pressure. Participants were 62 years old on average and 47% were men. The annual average PM2.5 level was 10 μg/m3. The investigators found linear relationships between ambient PM2.5 level and heart structure and function. Every 5 μg/m3 increase in exposure was associated with a 4-8% increase in left ventricular volume and a 2% decrease in left ventricular ejection fraction. Dr Aung said: "We found that as PM2.5 exposure rises, the larger the heart gets and the worse it performs. Both of these measures are associated with increased morbidity and mortality from heart disease." The researchers also looked for potential factors that could modify the relationship. They found that people with degree-level education were less prone to having a larger heart and had a smaller reduction in ejection fraction when exposed to PM2.5 than people with a lower level of education. Dr Aung said: "People who were highly educated were less likely to have harmful effects on the heart from pollution. This could be due to a number of factors including better housing and workplace conditions, which reduce pollution exposure. Educated people may also be more aware of their health, have healthier lifestyles, and have better access to healthcare." Regarding how pollution might have these negative effects on the heart, Dr Aung said PM2.5 causes systemic inflammation, vasoconstriction and raised blood pressure. The combination of these factors can increase the pressure in the heart, which enlarges to cope with the overload. The heart chamber enlargement reduces the contractile efficiency leading to reduction in ejection fraction. Dr Aung said: "We found that the average exposure to PM2.5 in the UK is about 10 μg/m3 in our study. This is way below the European target of less than 25 μg/m3 and yet we are still seeing these harmful effects. This suggests that the current target level is not safe and should be lowered." He continued: "Our results suggest that PM2.5 is linked with negative changes in the heart structure and function that are associated with poor outcomes. Reducing PM2.5 emission should be an urgent public health priority and the worst offenders such as diesel vehicles should be addressed with policy measures." In terms of what individuals can do to decrease their risk, Dr Aung said: "Avoid times and places where there is a high level of pollution. If you want to cycle into work and there is heavy traffic around that time then try to find a quieter route. Walk on the part of the pavement furthest from cars to reduce the amount of pollution you breathe in. Those with cardiorespiratory diseases should limit the time spent outdoors during highly polluted periods such as rush hours."


News Article | May 26, 2017
Site: www.greencarcongress.com

« Researchers find that high pressure is key to high-entropy alloys | Main | LA Metro awards multi-year contract for Clean Energy’s renewable natural gas to fuel CNG fleet » Research presented at the annual CMR (cardiovascular magnetic resonance) imaging conference of the European Association of Cardiovascular Imaging (EACVI) links PM pollution to heart damage. Among the sources of urban PM are diesel and gasoline direct injection (GDI) engines (earlier post). There is strong evidence that particulate matter (PM) from road vehicles is associated with increased risk of heart attack, heart failure, and death, said lead author Dr. Nay Aung, a cardiologist and Wellcome Trust research fellow, William Harvey Research Institute, Queen Mary University of London, UK. “This appears to be driven by an inflammatory response—inhalation of fine particulate matter (PM ) causes localized inflammation of the lungs followed by a more systemic inflammation affecting the whole body. “ The current study examined whether PM may damage the heart directly. The study included 4,255 participants from the UK Biobank, a large community-based cohort study. Cardiac magnetic resonance imaging was conducted to measure left ventricular volume (structure) and left ventricular ejection fraction (function). Annual average exposure to PM was calculated based on participants’ home address. The association between PM exposure and heart structure and function was estimated using multivariable linear regression, a form of statistical modeling which adjusts for potential factors that could influence the relationship such as age, gender, diabetes and blood pressure. Participants were 62 years old on average and 47% were men. The annual average PM level was 10 μg/m3. The investigators found linear relationships between ambient PM level and heart structure and function. Every 5 μg/m3 increase in exposure was associated with a 4-8% increase in left ventricular volume and a 2% decrease in left ventricular ejection fraction. The researchers also looked for potential factors that could modify the relationship. They found that people with degree-level education were less prone to having a larger heart and had a smaller reduction in ejection fraction when exposed to PM than people with a lower level of education. People who were highly educated were less likely to have harmful effects on the heart from pollution. This could be due to a number of factors including better housing and workplace conditions, which reduce pollution exposure. Educated people may also be more aware of their health, have healthier lifestyles, and have better access to healthcare. Regarding how pollution might have these negative effects on the heart, Dr Aung said PM causes systemic inflammation, vasoconstriction and raised blood pressure. The combination of these factors can increase the pressure in the heart, which enlarges to cope with the overload. The heart chamber enlargement reduces the contractile efficiency leading to reduction in ejection fraction. We found that the average exposure to PM in the UK is about 10 μg/m3 in our study. This is way below the European target of less than 25 μg/m3 and yet we are still seeing these harmful effects. This suggests that the current target level is not safe and should be lowered. Dr Aung presented the abstract ‘Impact of fine particulate matter air pollutant on cardiac atrial and ventricular structure and function derived from cardiovascular magnetic resonance (CMR) imaging – evidence from the UK Biobank’ during the BEST Oral Abstracts session on 26 May.


Norling L.V.,William Harvey Research Institute | Dalli J.,Harvard University
Current Opinion in Pharmacology | Year: 2013

Microparticles represent an intercellular communication and delivery mechanism for the efficient and effective transfer of biological information. These cargo vectors contain packages of material selectively assimilated from their parental cell, which includes bioactive lipids, integrins, cytokines, enzymes, mRNA and micro-RNA that can reprogramme recipient cells. Elevated levels of circulating microparticles are associated with a number of cardiovascular and inflammatory pathologies making them useful biomarkers for disease activity. Yet their full contribution to disease pathogenesis and its timely resolution remains to be elucidated. An emerging notion is that microparticles originating from different cell types or because of differential stimuli can exert deleterious or protective immunomodulatory actions. Herein, we discuss the bioactions of various microparticle components including genetic material, proteins and lipids and how they influence cellular behavior and ultimately host immunity. © 2013 Elsevier Ltd. All rights reserved.


Nadkarni S.,William Harvey Research Institute | McArthur S.,William Harvey Research Institute
Current Opinion in Pharmacology | Year: 2013

The regulation of the immune response to infection or tissue damage is a complex interplay of multiple factors, but it has long been recognised that steroid hormones can exert powerfulmodulatory effects at all levels of the innate and adaptive immune systems. Although most attention has been paid to glucocorticoids given their widespread clinical use, it is becoming increasingly clear that sex steroid hormones, and in particular the principle female sex steroid oestrogen, exerts potent effects upon the immune response. In this review, we will discuss the latest findings on the impact of oestrogen upon various cellular components of the immune system, and how this hormone can offer new opportunities to pharmacologically harness the immune response. © 2013 Elsevier Ltd. All rights reserved.


Accumulating evidence indicates that stem/progenitor cells (SPCs) represent an important source of cells in atheromas and contribute to lesion formation and progression. We investigated whether matrix metalloproteinase-8 (MMP8) played a role in SPC migration and their recruitment into atheromas. We found that SPCs in atheromas expressed MMP8 and that MMP8 knockout significantly reduced SPC numbers in atherosclerotic lesions in apolipoprotein E (ApoE)-deficient mice fed a Western diet. Further in vivo experiments showed that ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(-/-) mice had fewer SPCs in atheromas and smaller lesions than ApoE(-/-)/MMP8(-/-) mice injected with stem cells isolated from bone marrows of ApoE(-/-)/MMP8(+/+) mice. Ex vivo experiments showed that MMP8 deficiency inhibited the ability of SPCs to migrate from the arterial lumen and the adventitia into atherosclerotic lesions. In vitro assays indicated that MMP8 facilitated SPC migration across endothelial cells and through Matrigel or collagen I. We also found that MMP8 cleaved a-disintegrin-and-metalloproteinase-domain-10 and that MMP8 deficiency reduced mature a-disintegrin-and-metalloproteinase-domain-10 on SPCs. Knockdown of MMP8 or incubation with the a-disintegrin-and-metalloproteinase-domain-10 inhibitor GI254023X decreased E-cadherin shedding on SPCs. The decrease in migratory ability of SPCs with MMP8 knockdown was reduced by incubation of such cells with culture supernatant from SPCs without MMP8 knockdown, and this compensatory effect was abolished by an antibody against soluble E-cadherin. MMP8 plays an important role in SPC migration and their recruitment into atherosclerotic lesions.


Smyth D.G.,William Harvey Research Institute
Journal of Molecular Endocrinology | Year: 2016

Many important fields of research had a humble origin. In the distant past, A J P Martin’s discovery that amino acids could be separated by paper chromatography and Moore and Stein’s use of columns for quantitative amino acid analysis provided the first steps towards the determination of structure in complex biologically active molecules. They opened the door to reveal the essential relationship that exists between structure and function. In molecular endocrinology, for example, striking advances have been made by chemists with their expertise in the identification of structure working with biologists who contributed valuable knowledge and experience. Advantage was gained from the convergence of different background, and it is notable that the whole is greater than the sum. In the determination of structure, it may be recalled that four of the world’s great pioneers (Archibald Martin, Rodney Porter, Fred Sanger and Vincent du Vigneaud) were acknowledged for their fundamental contributions when individually they were awarded the Nobel Prize. They foresaw that the identification of structure would prove of outstanding importance in the future. Indeed, study of the structures of β-endorphin and enkephalin and the different forms of opiate activity they engender has led to a transformation in our understanding of chemical transmission in the brain. © 2016 Society for Endocrinology Published by Bioscientifica Ltd.


Ortega-Gomez A.,Institute for Cardiovascular Prevention | Perretti M.,William Harvey Research Institute | Soehnlein O.,Institute for Cardiovascular Prevention
EMBO Molecular Medicine | Year: 2013

Resolution of inflammation is a coordinated and active process aimed at restoration of tissue integrity and function. This review integrates the key molecular and cellular mechanisms of resolution. We describe how abrogation of chemokine signalling blocks continued neutrophil tissue infiltration and how apoptotic neutrophils attract monocytes and macrophages to induce their clearance. Uptake of apoptotic neutrophils by macrophages reprograms macrophages towards a resolving phenotype, a key event to restore tissue homeostasis. Finally, we highlight the therapeutic potential that derives from understanding the mechanisms of resolution. © 2013.

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