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Programme 6
THE FIRST EVGN ANNUAL CONFERENCE HIGHLIGHTS ADVANCES IN
CARDIOVASCULAR RESEARCH
Scientists describe new techniques for the identification of molecular targets in
endothelial dysfunction, clinical trials on stem cell therapeutic angiogenesis, and the
development of a potential vaccine against heart disease.
PRESS RELEASE – December 13th, 2004
CAMBRIDGE, UK – What is the relationship between atherosclerosis and the immune response and what are the
possibilities for the development of a vaccine against cardiovascular disease? What role do stem cells play in
angiogenesis and what are the possible clinical applications of stems cells in cardiac recovery?
These are few of the topics that will be discussed during the First European Vascular Genomics Network
(EVGN) Conference, which starts today at New Hall College in Cambridge, UK. Chaired by British Heart
Foundation Professor Andrew Newby (Bristol, UK), 140 vascular biologists drawn from the 35 EVGN networked
laboratories and from the wider scientific community are taking part. “Some of Europe’s most eminent vascular
biologists are holding a series of plenary lectures,” Newby says. “Perhaps more importantly, however, there is a
unique series of highly focussed workshops, each of which is designed to reach a consensus on future approaches
to key areas of strategic scientific importance.” EVGN, a Network of Excellence funded by the European Union
within its Framework Programme Six, was implemented on January 1 st, 2004. “Consonant with the overall aims of
Framework Programme Six, the EVGN in general and the Conference in particular will also give emphasis to wider
social issues such as gender equality, communication of scientific progress to the general public and maximising
the exploitation of scientific breakthroughs through both large and small enterprises,” Newby adds.
EVGN promotes multidisciplinary interaction in the field of vascular biology by uniting 25 basic and clinical
institutions (encompassing 35 academic groups), 2 biotechnology companies and 1 management company, from
10 EU Member or Associated States. “The Conference will allow presentation and intensive discussion of frontier
research in vascular biology, in an effort to integrate research activities of all groups from the EVGN,” says EVGN
scientific coordinator Alain Tedgui, of INSERM (Institut National de la Santé et de la Recherche Médicale, Paris,
France). “The attendees will present their latest results pertaining to the three research focus areas of the EVGN:
endothelial dysfunction, atherosclerotic plaque rupture and therapeutic angiogenesis. Furthermore, state-of-the-art
lectures will be presented by worldwide recognized experts, on clinical perspectives of these three main research
areas”.
The first year’s results
The EVGN struggle against cardiovascular disease is fought mainly on “post-genomic ground”. By identifying and
analysing the genes and proteins – and their complex relationships – that are responsible for the onset of the
diseases, it will be possible to develop new effective drugs and therapies and new tools and methods of diagnosis.
To do so, EVGN can count on powerful human and technological resources. “We have combined resources and
expertise to examine human arteries and material from model systems and we have established state-of-the-art
facilities and expertise with standardized protocols and bioinformatics,” EVGN scientist Martin Bennett, of the
Division of Cardiovascular Medicine at the University of Cambridge (UK), says. “The first target genes have already
been identified using both genomic and proteomic screens and we have also established the model system
required to study their role in the cause of heart attack”.
Clinical trials on therapeutic angiogenesis and stem cells
Is it possible to improve cardiac recovery by enhancing the process of vessel growth? To test this possibility, EVGN
scientists in Frankfurt and Homburg are now carrying out clinical multi-centre trials on patients with acute
myocardial infarction. "We have started clinical trials to use the so called ‘Endothelial Progenitor Cells’ to enhance
vessel formation: this is an entirely new concept and represents the most innovative aspect in the research area of
stem cells and therapeutic angiogenesis,” EVGN scientist Stefanie Dimmeler, of the University of Frankfurt
(Germany), says.
Angiogenesis (from the Greek angêion = “vase”, and genesis = “birth”) is the science that studies the formation of
new vessels. Among its therapeutic applications, aimed at improving cardiac oxygenation and reducing heart
failure, innovative methodologies have been recently developed using Endothelial Progenitor Cells (EPC). These
adult stem cells, made in the bone marrow, can differentiate into cells of the endothelium and may directly
participate to the angiogenic process. In collaboration with other EVGN laboratories, Dimmeler set out to
characterise this mechanism. “We don’t know how EPC are regulated in patients and we want to understand how
they can differentiate into endothelial cells to form new blood vessels,” Dimmeler says. ”The EVGN laboratories are
now sampling 500 volunteers to characterise their EPC. By comparing the results obtained in both healthy
individuals and patients with heart failure, and by combining this study with our previous knowledge on embryonic
stem cells by the expert laboratory of Elisabetta Dejana, of the FIRC Institute of Molecular Oncology (Milano, Italy),
we might be able to enhance the process of vessel growth. Preliminary results show that patients with coronary
artery disease have less EPC than healthy volunteers.”
Identification of molecular targets in endothelial dysfunction
The endothelium is a thin layer of flat smooth cells that line the inner walls of blood vessels. The term “endothelial
dysfunction” reflects a state of endothelial cell activation in which, for example, blood flow-induced changes in
vessel diameter are attenuated and the expression of a number of pro-inflammatory proteins is enhanced. Since
this state is key to the atherosclerosis progression, the endothelium can be seen as an early therapeutic target, and
the maintenance of normal endothelial cell function would be expected to delay the vascular inflammation
associated with clinical symptoms. But the mechanisms resulting in endothelial dysfunction have yet to be fully
characterised. “We know for example that the very same stimuli that elicit an increase in blood flow in a healthy
vessel do quite the opposite during the development of atherosclerosis. Our goal is to determine why and how the
functions of the endothelial cells change during the atherosclerotic process,” EVGN scientist Ingrid Fleming, of the
University of Frankfurt (Germany), says. “The idea is to find critical molecular targets that could then become
therapeutic ones. Many of our partner laboratories are actively involved in the identification and characterisation of
the proteins that play a crucial role in endothelial dysfunction. A particularly important emphasis is being placed on
identifying enzymes within the blood vessel wall that generate ‘free radicals’ [highly reactive molecules that can
damage and destroy the cell structures] which previous studies have found to be connected with the dysfunction.
One of the main objectives of EVGN in this area is to develop and implement new standardised protocols for target
identification, to be applied in all European laboratories. “We are currently using a quite advanced technique, that
combines biochemistry and in vivo experiments in animal models,” Fleming says, “Thanks to this highly efficient
technique, we hope to be able to gather a lot of information in a limited amount of time.”
Immune responses discovered in atherosclerosis may be used to develop a vaccine against heart disease
The laboratory of Göran K. Hansson, at Karolinska Institutet (Stockholm, Sweden) is contributing to the EVGN
research activities on the double frontline of atherosclerosis therapy and prevention. Atherosclerosis, the hardening
of the arteries caused by accumulation of fatty deposits (plaques) and other substances, is the main cause of
arterial thrombus (blood clot) formation, coronary artery occlusion and heart attack. But scientists have found a
weak point in this too often lethal disease: atherosclerosis is an inflammatory process and as such could be treated.
“Several research groups in Europe and in the United States have reported that immune responses are involved in
atherosclerosis,” Hansson says. “However, only now it has been realized that the inflammation elicited by the
atherosclerotic plaque is the key factor that will eventually precipitate thrombosis and infarction.”
Hansson has studied patients with atherosclerosis and identified T cells (immune cells) that recognize cholesterol
particles (lipoproteins). “Oxidation of these lipoproteins in the blood vessels causes chemical changes in the
particles, which are now recognized by the immune system as if they were pathogenic microbes. We have found
that immunization of experimental mice with oxidized lipoproteins protects the animals against the development of
atherosclerosis,” Hansson explains. “This may open up a new possibility to prevent heart attacks and stroke by
vaccination.”
On the therapy frontline, Hansson is currently studying the mechanisms that regulate the immune response to
atherosclerosis. “Working together with the EVGN team lead by Alain Tedgui, in Paris, we have observed that
activated immune cells can produce signal molecules, called ‘cytokines’, that dampen the atherosclerotic process,
Hansson adds. “These molecules might be very interesting targets for future therapy, to reduce the risk of stroke.
There is a lot to learn, but we are on our way and our preliminary results are promising.”
Vascular Biology in Europe: the key role of EVGN
Vascular Biology is the basic science discipline that underpins increased understanding and new treatments for
coronary heart disease, stroke and other cardiovascular diseases. “These collectively account for more deaths in
people of working age than any other group of diseases,” Conference chairman Andrew Newby explains.
“Moreover Vascular Biology makes an important contribution to understanding the growth of tumours, which like all
tissues need an adequate blood supply.” Hence Vascular Biology also plays a relevant role in the study of cancer,
the other major killer of younger people. And there is more: “Vascular Biology is the scientific basis for much of the
biotechnology and pharmaceutical industry activity related to these diseases and hence an important contributor to
wealth creation in this sector, as well as health, in Europe,” Newby adds.
Despite its importance, Vascular Biology has lacked a collective voice at European level. “This has happened,”
Newby explains, “partly because the discipline is bigger than one disease area. Vascular Biology is also farther
from the ‘market’ than areas such as Cardiology, Radiology and Diabetology, for example, all of which have
powerful European professional organisations funded for the most part by firms that service these clinical activities.”
In recognition of these limitations, part of the brief of the EVGN is to permanently restructure the field of Vascular
Biology in Europe. EVGN is working with established groups such as the European Vascular Biology Organisation
to make the leap to democratically representing the interests and aspirations of European vascular biologists. In its
first year, the EVGN has built a Web based communication platform (http://www.evgn.org) and undertaken detailed
planning for the first summer school, to take place in 2005. In addition, it is directly funded to establish a wider
communications network among vascular biologists, a summer school for young vascular biologists in training, and
a series of European Vascular Biology Research Conferences.
CONTACTS
Andrew C. Newby
First EVGN Conference Chairman
Bristol Heart Institute, Bristol Royal Infirmary, Bristol BS2 8HW
Phone: +44 (0) 1179 283 582
Fax: +44 (0) 1179 283 581
E-mail: [email protected]
Alain Tedgui
EVGN Coordinator
Inserm U541, 41 bd. De la Chapelle, 75475 Paris cedex 10, France
Phone: +33 1 4463 1866
Fax: +33 1 4281 3128
E-mail: [email protected]
Press contacts:
Francesca Noceti and Ilaria Fazi
IFOM – The FIRC Institute of Molecular Oncology Foundation
Press Office and Communication
EVGN Outreach to the general public
Phone: +39 02 574303206 - +39 02 5693063
Mobile ph.: +39 339 1779787 (F. Noceti)
Mobile ph.: +39 349 2305441 (I. Fazi)
E-mail: [email protected]
Additional information on the EVGN is available at http://www.evgn.org/
Please find attached the complete program of the First Annual EVGN Conference
EVGN partner Institutions
1. Institut National de la Santé et de la Recherche Médicale,
France
2. University of Bristol, United Kingdom
3. Johann Wolfgang Goethe-Universität, Frankfurt, Germany
4. Chancellor, Master and Scholars of the University of
Cambridge, United Kingdom
5. Cardiovascular Research Institute of Maastricht, Netherlands
6. Karolinska Institutet, Sweden
7. The FIRC Institute of Molecular Oncology Foundation, Italy
8. University of Zürich, Switzerland
9. Medical University Vienna, Austria
10. Universitätsklinikum Eppendorf, Germany
11. University of Saarlandes, Germany
12. Vrije Universiteit Medical Center VUmc, Netherlands
13. Leiden University, Netherlands
14. Academic Medical Center, University of Amsterdam,
Netherlands
15. Vita-Salute San Raffaele University, Italy
16. Medizinische University of Innsbruck, Austria
17. University of Kuopio, Finland
18. University of Torino, Italy
19. National Institute of Biostructures and Biosystems, Italy
20. St. George's Hospital Medical School, United Kingdom
21. The Hebrew University of Jerusalem, Israel
22. The University of Birmingham, United Kingdom
23. University College London, United Kingdom
24. University of Geneva, Switzerland
25. Centre Européen de Recherche en Biologie et en Médecine
(GIE), France
26. Ark Therapeutics Ltd, United Kingdom
27. Technoclone GmbH, Austria
28. Inserm-Transfert SA, France