“Although we have very high quality cardiovascular science in Europe, a suitable forum has been lacking,” explained Professor Axel Pries, Chairperson of FCVB 2010, adding that while the main ESC Congress has always included strong basic science components, limits have been placed on the number of sessions included. “FCVB will be a comprehensive meeting looking at the cutting edge science to expose delegates to the full array of current thinking. It’s needed to maintain and develop the standards of cardiovascular science in Europe.”
There has been a growing realisation, said Professor Raffaele De Caterina, chairman of CBCS that innovations in cardiovascular therapy come largely as a direct by-product of research in basic science. “This emphasised to us the need to promote basic science,” he said.
The conference should provide delegates with excellent opportunities for networking. “The really wide and varied programme provides a unique opportunity to meet people from different fields, join forces and create common solutions. Bringing people together should create an explosive cocktail that’ll help find solutions for many of the challenges we’re facing,” said De Caterina.
An additional benefit of establishing a strong cardiovascular scientific meeting in Europe is that it will help boost career options, and stem the brain drain. “Improving science communications in Europe can only help publicize career options, and allow people to learn about possibilities closer to home,” said Pries.
FCVB, which is predicted to attract over 600 attendees, will be held at the Anatomy Institute of Charité Universitätsmedizin, Berlin. “The choice of setting was deliberate – it’s both cost effective and makes for a relaxed academic atmosphere that should particularly help to put younger delegates at ease,” said Pries.
The conference is placing particular focus on the needs of young cardiovascular scientists. “We want to help them explore the scientific landscape and find out where their particular interests lie. This is a make and break stage of their careers. If we can help set them on the right path they’ll be more likely to stay in cardiovascular science,” said Pries.
The translational component of the programme should make the meeting of great interest also to clinicians. “Advances in cardiology are driven by good interactions between clinicians and basic scientists, with clinicians setting the questions that basic scientists then try to answer. Without their involvement we would be operating in an ivory tower,” said Pries.
The scientific programme will feature 80 invited talks and over 400 abstracts. One highlights of FCVB will be the opportunity to hear world class leaders in their fields delivers key note lectures. E Marban (Los Angeles, US) will talk about stem cells in perspective; GA FitzGerald (Philadelphia, US) about drugs, industry and academia; K Alitalo (Helsinki, FI) about the molecular regulation of angiogenesis and lymphangiogenesis, N Rajewsky (Berlin, DE) about post-transcriptional gene regulation by small RNAs and RNA binding proteins, and P Libby (Boston, US) about inflammation in atherosclerosis.
Three parallel scientific sessions will run, providing everyone with opportunities to hear the latest developments in their own fields, with time scheduled for the best abstracts to be presented both within the pre-arranged symposia and in two oral award sessions. “My dream is that young people doing bench work will come to think of FCVB as an opportunity to show cases their work before international audiences,” said Pries.
One noteworthy event at the start of the meeting is the “Ursula Ravens: Commitment to the heart session”, which will honour the life-time work of electro physiologist Ursula Ravens, head of the Department of Pharmacology and Toxicology at the University of Dresden, now approaching retirement. Here, talks on Professor Ravens’ work in the field of calcium homoeostasis and excitation contraction coupling will be delivered by DA Eisner (Manchester, UK), adrenoceptor control of the heart by Sian Harding (London, UK) and regenerative approaches for the treatment of cardiac diseases by T Eschenhagen (Hamburg, DE).
“Ursula’s work has demonstrated a wonderful combination of being extremely rigorous and precise, but at the same time very creative. She embodies what’s good about translational medicine in the sense that everything is rooted in the very best basic science,” said Professor Sian Harding, from Imperial College, London, who will be introducing the session. “It’s a testament to Ursula’s popularity that everyone wanted to organise this festival of her work. She’s really energised the field and brought people together.”
In keeping with the youthful theme of the meeting, a lively social programme will be offered, including a Get Together Party on the first night and a Dinner-show in a variety theatre on the last night.
Boosting cardiovascular drug development
The current model of drug development is out of date, inefficient and unsustainable, said Garret FitzGerald, director of the Institute for Translational Medicine and Therapeutics at University of Pennsylvania. Furthermore, the development of new therapies in the arena of cardiovascular disease has fallen behind other therapeutic areas. A recent analysis of 16,000 peer reviewed journal articles, by SciBX, revealed that cancer comprised 32 % of all translational research tracked, with neurology and infectious diseases each following at about 15 % and endocrine and cardiovascular diseases coming in at 9 % and 6 % respectively. Such priorities exist despite the fact that the majority of disease related deaths worldwide are from cardiovascular causes.
In his key note lecture at FCVB, FitzGerald will make the case for revolutionary change in the organisation of cardiovascular research. “The problem has not been identifying drug targets, where combinatorial chemistry and high throughput screening have been extremely successful. Instead, the difficulty has been in unsustainable business models for the development of new therapeutics,” he said.
The conventional model of drug development within large vertically integrated Pharma companies is outmoded, he said, and needs to be replaced by a more segmented model transcending sectors and national boundaries. “The concentration of expertise required isn’t likely to arise in one pharma company, biotech company or academic medical centre. It’s likely to be scattered around different institutions, leading to a new era of academic drug development.”
The introduction of such change will result in the need to share information in a secure way across different sectors and national boundaries. “This will require a substantial revision of the ground rules regarding intellectual property and imaginative and transparent approaches to the disclosure and “management” of conflicts of interest,” he said.
A particular problem, added FitzGerald, has been the demise of clinical pharmacology as an academic discipline. “There is now a critical lack of people with human pharmacology expertise in academia, industry and regulatory bodies,” he said.
To overcome these difficulties there was a need for re branding of the discipline into Translational Medicine and Therapeutics (TMAT), with the support of government initiatives. Recently the Wellcome Trust put out a call for training in translational research and therapeutics. Such initiatives, hopes FitzGerald, will enable the next generation to get up to speed in the area.
“Change won’t happen in a coordinated fashion, but through a myriad of local initiatives. As people begin to see how well these processes work they’ll be increasingly adopted,” he said.
New therapeutic approaches to targeting vulnerable plaques
Ira Tabas from Columbia University (New York, USA), will provide insights into the “maladaptive inflammatory response” that may account for transition of sub clinical atherosclerotic lesions into dangerous vulnerable plaques in the symposium “Dissecting the Vulnerable Plaque” on Sunday.
Initially atherogenesis is triggered by retention of apolipoprotein B containing lipoproteins in the sub endothelium of the arterial wall. The presence of lipoproteins triggers a chronic inflammatory response involving macrophages and T cells. “Normal inflammatory responses are followed by a resolution phase in which inflammatory cells go away and debris gets cleared up,” explained Tabas, "but this resolution response appears to fail in certain percentage of atherosclerotic lesions, likely due to defects in specific molecular and cellular events, and this failure may be a leading mechanism behind vulnerable plaque formation.”
Notably defects in a key process in inflammation resolution, efferocytosis (the clearance of apoptotic cells by phagocytes), leads to post-apoptotic secondary necrosis, which amplifies the inflammatory response and results in the creation of vulnerable plaques. “One of the reasons people may be genetically predisposed to heart disease could be due to difficulties with their efferocytosis response or with other inflammation resolution responses,” suggested Tabas.
The process of efferocytosis is known to involve a complex interplay between several sets of proteins that enable both recognition and engulfment of apoptotic cells by phagocytes. The MerTK protein found on the surface of phagocytes, for example, is known to interact with apoptotic cells and to be susceptible to cleavage by certain enzymes, thereby inhibiting efferocytosis. Indeed, knock-out mice lacking the MerTK protein have been shown to have decreased efferocytosis and increased inflammation and plaque necrosis.
“The billion dollar question is why some people aren’t undergoing effective efferocytosis,” said Tabas, who will provide details on some of the potential therapeutic strategies that are being considered to address the problem. Whatever the chosen therapy, there are still likely to be technical challenges involved with administering the bio-active protein in a plaque targeted manner. New approaches, such as nanoparticle-based therapy, may provide the solution, suggested Tabas.