Vascular Aston

The home of Vascular Research at Aston University, with a focus on Angiogenesis and Vascular Protection. Seeking to improve Social Mobility by widening participation in Higher Education.

Welcome

Welcome to Vascular Aston, the home of Vascular Research at Aston University, Birmingham.

Please refer to the ‘About‘ section for information concerning the Vascular Aston team and the work we do, our objectives and values, links to our recent publications and team member profiles. The home page will regularly be updated with details of our recent findings and information about future research projects, so you can stay up to date with the latest developments in Vascular Medicine.

We will also be sharing our views on Social Mobility and discussing the work done by Aston University to encourage widening participation in Higher Education as a means to address social deprivation and health inequalities within local communities. Through this page you will be able to follow the latest developments in Aston’s widening participation strategy and learn about how our future initiatives will help to transform the lives of local people.

Preeclampsia Breakthrough from Aston University

A brief summary of our “ground-breaking study”

Preeclampsia is the most common serious pregnancy complication, affecting 4-8% of all pregnancies worldwide with potentially severe consequences for both mother and baby. The Vascular Research team at Aston University have a wealth of experience in preeclampsia study, and much of our work is focused on trying to elucidate the etiology of this complex condition and developing new therapies to ameliorate it’s effects.

In June 2013 the results of our most recent study into preeclampsia were published in the preeminent cardiovascular journal Circulation. The study examines the role of Hydrogen Sulfide, a naturally-occurring gas known for it’s “rotten egg” odour, in the development of preeclampsia. The findings of this research project are potentially extremely significant; in addition to identifying a novel factor contributing to the development of preeclampsia symptoms, it presents the possibility of developing an effective treatment for the disorder within the near future. It was described by Circulation as being a “ground-breaking study”, and has also received mainstream media attention.

The images below are taken from a presentation about the aforementioned research study and concisely summarise our aims and findings.

Click on individual slides to view them full-screen.

H2S Poster Page 1

H2S Poster Page 2

H2S Poster Page 3

H2S Poster Page 4

Related Links:

 

Circulation Logo

Widening Participation in Higher Education

In addition to maintaining a strong focus on high-quality research work, Aston University is committed to widening participation in higher education. The University seeks to ensure that it is truly representative of the community it serves and that students from all backgrounds are given the opportunity to receive a first-class education.

Grauates - Widening Participation

“Aston’s policy has been to expand and widen participation without compromising academic standards. The University’s impressive track record in widening participation is one of which we are extremely proud. In 2007/08, 57% of new entrants were from ethnic minorities, 91.4% were from state schools/colleges, 11.3% were from low participation neighbourhoods, and 2.3% were in receipt of Disabled Students Allowance. Aston’s Widening Participation Strategy has been to provide support to students throughout the student life cycle, from aspiration raising in primary schools through to student graduation and employment”

At Aston we are constantly striving to approach social inequalities in new and innovative ways, providing access to education for students from hard-to-reach areas with the aim of improving routes into employment and benefiting local communities. We feel passionately about social deprivation and are keen to address health inequalities within society; we believe that one of the ways in which we can help to improve the quality of life experienced by residents of low-income areas is to facilitate the training of medical professionals from these localities.

In the future we hope to help more individuals from low-income backgrounds receive the best possible training, making higher education and the medical profession more accessible and socially representative. In doing so we hope to improve social mobility prospects and reduce the effects of social deprivation by improving local healthcare.

Widening participation is an issue we feel strongly about. We aim to improve access to education and stimulate social mobility, redressing the inequalities that exist throughout our society. Follow Vascular Aston for regular updates about our latest initiatives, and our take on social mobility issues in the UK.

“Aston University makes a strong commitment to Social Mobility”

Aston University Campus

Aston University’s Access Agreement and Scholarships Programme has been approved by the Office for Fair Access (OFFA) for students joining the university in 2014-15.

Aston’s access agreement continues the Institution’s success of promoting Accessible Excellence in supporting students from a wide range of backgrounds.

Key Elements of Aston’s commitments for 2014 -15 include:

  • Aston’s highly regarded sandwich placement year or year abroad will be heavily subsidised at £1,000 with most Aston students receiving a scholarship to reduce the fee to zero. Over 50% of Aston students take this potentially life-changing opportunity to gain industry experience in the UK or abroad. The Aston placement year is a significant contributor to Aston’s outstanding record for graduate employability.
  • Aston’s Languages for all programme allows all new students to learn a foreign language for free giving them access to global skills networks and awareness.  Options include French, German, Arabic, Japanese, Portuguese and Mandarin Chinese.
  • A range of scholarships to support students with their living costs, accommodation or tuition fees.
  • Most Aston Scholarships include a choice of how the award is taken, giving our students greater flexibility. Scholarships are based on family income and include Excellence Scholarships for students who achieve AAB or equivalent at A level.  Aston Scholarships are typically worth between £500 and £3,000 in first year and beyond.
  • Significant investments in outreach activities with Schools and Colleges. This includes further support for Primary School students to aim for University. For example Aston supports the City of Birmingham Children’s University and hosts Graduation ceremonies for over 500 primary school pupils every year. Over 25,000 prospective students, parents and teachers visited Aston’s campus in 2012-13 for outreach and aspiration raising events.

The Aston University commitment aims to be one of the boldest and best at promoting widening participation. At the moment over 90% of Aston students come from state schools, and 35% are from the lowest four socio-economic groups.  Aston is one of only a handful of Universities in the UK’s top 30 to consistently exceed its government benchmarks on social inclusion.

This article appears in its original format here on the Aston University website. If you would like to know more about our efforts to widen participation and improve social mobility prospects, see here. Follow Vascular Aston for regular updates about our widening participation initiatives, and our take on social mobility issues in the UK. 

Vascular Research at Aston University

Aston University Main Building

The Vascular Research team is relatively new to Aston University; however it has already made a significant contribution to Aston’s research output (see here). Our research interests are primarily focused on the vascular basis of diseases, particularly in the areas of angiogenesis (how new blood vessels form from pre-existing vessels) and vascular protection.

We are committed to translational research (“from bench to bedside”) with a view to develop our discoveries from invention through to practical application, maintaining a clear focus on helping people affected by the conditions we study. Through our research we hope to understand the pathogenesis (origins) of vascular diseases such as preeclampsia and arthrosclerosis and to develop therapeutic interventions based on our findings.

The team is led by Asif Ahmed, Professor of Vascular Biology and Pro-Vice-Chancellor for Health at Aston University. Prof Ahmed has an international reputation in angiogenesis and vascular protection research and is known for producing world-leading research in his area of expertise. He is joined as part of the Vascular Aston team by Dr Shakil Ahmad, Dr Keqing Wang and Dr Meng Cai.

Our current research projects are focused particularly on preeclampsia, taking a multi-dimensional approach to evaluating potential causes of the disorder and developing new therapies based on our findings. The team has a wealth of experience between them and our collective research strategy is based on years of academic study, its direction having been influenced by a number of key discoveries along the way.

In 2000, Prof Ahmed discovered that an enzyme called placental Heme Oxygenase (HO) protects the human placenta against injury. He went on to identify carbon monoxide (CO), the gaseous product of HO, as an inhibitor of two anti-angiogenic proteins (soluble Flt-1 and soluble endoglin). Soluble Flt-1 has been increasingly recognized as a major factor responsible for the clinical signs of preeclampsia. In 2004 Ahmed & Ahmad identified soluble Flt-1 as the single most important molecule responsible for angiogenic imbalance in preeclampsia, by demonstrating that the removal of sFlt-1 from preeclamptic samples restored angiogenic balance.

In a 2007 study, Prof Ahmed’s team discovered that increasing heme oxygenase activity could provide protection against preeclampsia. This discovery has formed the basis for the world’s first randomized controlled clinical trial on the use of statins in pregnancy, the StAmP Trial, which is currently ongoing at Aston University. This trial aims to determine whether statins can be used effectively to ameliorate the symptoms of early-onset preeclampsia. If successful, it could allow serious cases of preeclampsia to be treated using drugs which are already widely available, and could be the first major step towards curing preeclampsia altogether (see here).

Vascular Research Poster

The Vascular Aston team recently identified another diatomic molecule, hydrogen sulfide (H2S), as offering the potential to treat both preeclampsia and fetal growth restriction in pregnancy. These findings have been published in the prestigious scientific journal Circulation and were highlighted as being “groundbreaking” both by Circulation and within the mainstream media. This is the first time two naturally-occurring small gaseous molecules (CO and H2S) have been shown to prevent the release of the culprit proteins (sFlt-1 and sEng) which are elevated in preeclampsia. More importantly, in this new work we have shown that it is possible to restore fetal growth and fix the vascular abnormalities (angiogenesis) in preeclamptic placenta by restoring hydrogen sulfide levels.

The Vascular Aston team will continue to evaluate the effects of anti-angiogenic growth factors that contribute to vascular disorders, in particular preeclampsia, and develop therapeutic targets for these conditions. The ongoing StAmP trial and our research into the effects of hydrogen sulfide are both promising avenues which we will continue to pursue, with the aim of developing novel therapies for preeclampsia. We hope that before the end of the decade our research will allow us to develop a single treatment for the condition that will change clinical approaches to managing preeclampsia for future generations.

World-Leading Research Output from Aston University

LHS 4* Research Word Cloud

The REF (Research Excellence Framework) is a method for objectively assessing the research output of British higher-education institutions, grading publications based on their overall quality and the importance of their findings. The maximum 4* rating is awarded to those publications classed as being “world-leading in terms of originality, significance and rigour”.

The word cloud above depicts the relative frequency with which specific terms have appeared in the titles of 4* research papers, defined as key words within these papers, or identified as MeSH terms (Medical Subject Headings) on PubMed. The largest words are those that appear most frequently across these three fields. It includes every 4* research publication produced by members of the School of Life & Health Sciences at Aston since 2008.

Despite being relatively new to the University (2012), the Vascular Research team has made a significant contribution to Aston’s research output; note the prominence of terms such as Vascular, Preeclampsia, Endothelial and VEGF (Vascular Endothelial Growth Factor). The Vascular Aston team are proud to be contributing to the University’s burgeoning reputation as a world-leading research institution, and we hope that our current and future projects will help to further extend this reputation over the coming years.

“Aston researchers help fight life-threatening pregnancy condition”

Pregnancy

Scientists at Aston University have found that hydrogen sulfide, a compound known for its rotten egg odour, could be key to helping prevent life threatening conditions during early pregnancy.

Pre-eclampsia is a condition that affects one in 20 first-time mothers towards the end of pregnancy. The chemical substance is formed naturally in the body, and produces different levels among some women with some producing less than others.

These changes lead to complications for the woman such as high blood pressure and can damage the kidneys and liver. Pre-eclampsia can develop into eclampsia, a type of seizure that can be fatal.

Initial tests carried out by Aston University researchers revealed that giving hydrogen sulfide to pregnant women could block the release of two chemicals that increase blood pressure in the mother and protect the growth of their babies. The discovery could lead to a treatment for pregnant women being developed by the end of the decade. This will be in pill form because the gas in its natural form is toxic.

Around 20 women die each year from conditions linked to high blood pressure including pre-eclampsia, while around 600 babies a year die as a result of pre-eclampsia. The only treatment currently available is to deliver the baby early with an emergency caesarean.

Professor Asif Ahmed, of vascular biology at Aston University, who lead the researcher, said;

“Our findings show that we can restore foetal growth and fix the vascular abnormalities in the placenta that cause pre-eclampsia by giving back hydrogen sulfide. This is significant because it opens up new therapeutic and diagnostic potential for tackling the disorder in its early stages.

He added;

“I am confident that we will have a viable therapy for pre-eclampsia and foetal growth restriction by the end of this decade based around these discoveries. By using drugs to prevent the release of the chemicals that damage the lining of blood vessels in the mother and the placenta, we could provide an effective therapy for pre-eclampsia”

The research is published in the medical journal Circulation, which described it as ‘ground-breaking’. Following the recent discovery future research will now build on this initial research to explore ways the condition could either be treated or prevented.

You can view this article in its original format on the official website of Aston University. The original research paper that is the subject of the article can be found here.

The latest Preeclampsia research findings from Vascular Aston

Below you can find the abstract taken from our recent paper on preeclampsia, which was published in the prestigious scientific journal Circulation:

Circulation Logo

Dysregulation of Hydrogen Sulfide Producing Enzyme Cystathionine γ-lyase Contributes to Maternal Hypertension and Placental Abnormalities in Preeclampsia

Keqing Wang, MD, PhD; Shakil Ahmad, PhD; Meng Cai, PhD;Jillian Rennie, BSc; Takeshi Fujisawa, PhD; Fatima Crispi, MD, PhD;James Baily, MD; Mark R. Miller, PhD; Melissa Cudmore, PhD;Patrick W. F. Hadoke, PhD; Rui Wang, MD; Eduard Gratacós, MD;Irina A. Buhimschi, MD; Catalin S. Buhimschi, MD; Asif Ahmed, PhD

Abstract

Background: The exact etiology of preeclampsia is unknown, but there is growing evidence of an imbalance in angiogenic growth factors and abnormal placentation. Hydrogen sulfide (H2S), a gaseous messenger produced mainly by cystathionine γ-lyase (CSE), is a proangiogenic vasodilator. We hypothesized that a reduction in CSE activity may alter the angiogenic balance in pregnancy and induce abnormal placentation and maternal hypertension.

Methods and Results: Plasma levels of H2S were significantly decreased in women with preeclampsia (P<0.01), which was associated with reduced placental CSE expression as determined by real-time polymerase chain reaction and immunohistochemistry. Inhibition of CSE activity by DL-propargylglycine reduced placental growth factorproduction from first-trimester (8–12 weeks gestation) human placental explants and inhibited trophoblast invasion in vitro. Knockdown of CSE in human umbilical vein endothelial cells by small-interfering RNA increased the release of soluble fms-like tyrosine kinase-1 and soluble endoglin, as assessed by enzyme-linked immunosorbent assay, whereas adenoviral-mediated CSE overexpression in human umbilical vein endothelial cells inhibited their release. Administration of DL-propargylglycine to pregnant mice induced hypertension and liver damage, promoted abnormal labyrinth vascularization in the placenta, and decreased fetal growth. Finally, a slow-releasing H2S-generating compound, GYY4137, inhibited circulating soluble fms-like tyrosine kinase-1 and soluble endoglin levels and restored fetal growth in mice that was compromised by DL-propargylglycine treatment, demonstrating that the effect of CSE inhibitor was attributable to inhibition of H2S production.

Conclusions: These results imply that endogenous H2S is required for healthy placental vasculature and that a decrease in CSE/H2S activity may contribute to the pathogenesis of preeclampsia. (Circulation. 2013;127:2514-2522).

If you’re interested by what you have read and would like to learn more, you can view this article online in its entirety at Circulation or via PubMed. Please don’t hesitate to share your thoughts with us – we’re always eager to receive feedback and discuss our research.

Testing Potential Preeclampsia Therapies – The StAmP Trial

StAmP Logo

StAmP stands for ‘Statins to Ameliorate early-onset Pre-eclampsia’ and is the title of an ongoing clinical trial initiated by our Vascular Research team. It is the world’s first randomized controlled clinical trial on the use of statins in pregnancy, and has the potential to completely transform the way we treat preeclampsia.

Statins are a class of drugs commonly taken by individuals prone to heart disease. They are currently used to lower cholesterol in patients at risk of heart disease and work by inhibiting cholesterol-producing enzymes in the liver. Research has shown that statins have a pleiotrophic (multi-faceted) effect; in pre-clinical trials conducted by Vascular Aston researchers they have been shown to reduce the two proteins which were previously identified as being elevated in patients with preeclampsia.

The effects of Pravastatin are currently being tested on patients diagnosed with early-onset preeclampsia recruited from 15 centres around the UK. StAmP is a “double-blind, randomised placebo-controlled” trial, meaning that in the interest of accuracy and objectivity, neither the doctor responsible for administering the treatment nor the patient know whether they have been given statins or a placebo for the duration of the trial.

If this trial is successful it could allow us to treat serious cases of preeclampsia effectively using drugs which are already widely available, and could potentially be the first step towards curing preeclampsia altogether.

You can read more about the StAmP Trial via the following links:

An Introduction to Preeclampsia

preeclampsia image

Hypertension (high blood pressure) is the most frequently occurring medical problem experienced by mothers during pregnancy. Preeclampsia (also written as pre-eclampsia) is the most common serious pregnancy complication, affecting 4-8% of all pregnancies. It is a de novo (i.e. not linked to pre-existing disorders) hypertensive syndrome, which if left untreated can develop into Eclampsia, an extremely dangerous and often fatal condition characterized by blood-clots and seizures.

The Preeclampsia Foundation states that:

“Globally, preeclampsia and other hypertensive disorders of pregnancy are a leading cause of maternal and infant illness and death. By conservative estimates, these disorders are responsible for 76,000 maternal and 500,000 infant deaths each year.”

As is evident from the statement above, preeclampsia is a major contributor to maternal and fetal morbidity and mortality worldwide. The British charity Action on Pre-eclampsia (APEC) estimates that:

“Every year in the UK about 1000 babies die because of pre-eclampsia – many of these as a consequence of premature delivery rather than the disease itself. Some 7 mothers die each year from complications of pre-eclampsia in the UK.”

Preeclampsia is characterized by high blood pressure (hypertension), fluid retention (oedema) and excessive protein levels in the urine (proteinuria). These symptoms are not evident during the early stages of pregnancy and as such preeclampsia can be difficult to diagnose. It is only detectable by regular antenatal checks on maternal blood pressure and urine, and as such women without access to adequate healthcare services are particularly at risk.

There is currently no way of curing preeclampsia. In severe cases the only way to relieve the mother’s symptoms is to artificially induce delivery or to prematurely deliver the child by emergency caesarian section. Being born prematurely can have serious consequences and every year four million babies are born with fetal growth restriction as a consequence of preeclampsia.

Although preeclampsia has been the subject of scientific research for many years, the exact etiology of the condition is as yet unknown. Recent research has indicated that the poor development of placenta may be responsible, preventing the transfer of nutrients from mother to baby that are essential to its healthy development. Through our research we aim to find out specifically what it is that causes preeclampsia and to identify methods for earlier diagnosis of the condition, allowing us to manage it more effectively. Ultimately we hope to develop a safe and effective therapy for preeclampsia and reduce the risk it poses to mothers and children around the world.