A breakthrough towards preventing cardiovascular diseases
The hardening of arteries - also known as 'atherosclerosis' - can cause cardiovascular diseases (CVD), which can lead to heart attacks and strokes. New evidence has been uncovered strengthening the link between inflammation - a defensive reaction of the body - and cardiovascular diseases. This could lead to new innovative preventive and therapeutic strategies, and perhaps ultimately to a cure for atherosclerosis.
'Atherosclerosis' is a chronic and slowly progressive pathological condition involving the inflammatory system. It leads to an accumulation of plaque – containing fatty materials and inflammatory cells – in the walls of the arteries. Complications from advanced atherosclerosis can cause CVD, leading to a heart attack or stroke. Every year, CVD causes over 4 million deaths in Europe – i.e. nearly half of all deaths.
The EU-funded Atheromoto project has opened up the possibility of finding new effective treatments by developing a genetically modified mouse model that mimics patients with aggressive inflammatory diseases which display symptoms of atherosclerosis.
“Using the latest tools of molecular biology and proteomics [the study of proteins, which perform important functions within the body], we have identified molecular targets [for possible future therapies] of the immune system in the arterial vessel walls,” explains project researcher Aksam Merched. “We were able to come up with some missing puzzle pieces related to our understanding of how CVD is caused.”
Dr Merched believes that the findings could lead to the development of innovative preventive and therapeutic approaches, which could ultimately bring a cure for atherosclerosis and help save millions of lives. “Obviously, clinical validation of these discoveries is a prerequisite to any translational application in patients,” he says.
The long-term goal is to better understand the cellular and molecular immune basis of cardiovascular disease, and to identify the molecules on which scientists need to focus in order to develop effective new treatments and therapies. The project’s objective is to help design novel immunotherapies to prevent heart attacks and strokes or cure patients who have suffered them.
Investigating origins of inflammation
Inflammation is a double-edged sword. It is an important and necessary biological reaction, usually triggered by the body to ease pain and initiate the healing process. Left unabated, however, it can cause progressive destruction of tissue, leading to many diseases.
Although the inflammatory aspect of cardiovascular diseases is now well recognised, current knowledge of the causes of this inflammatory reaction has been somewhat limited. Moreover, the exact nature of internal vascular stimuli that trigger immune responses has not yet been fully researched. One reason for this deficit is the lack of an appropriate animal model, which is something the Atheromoto project has addressed.
Several studies have shown that atherosclerotic patients develop a perturbed inflammation in their arteries, suggesting that autoimmune processes – the failure of an organism to recognise its own constituent parts – may play a role in the development of atherosclerosis.
The project’s mouse model combined autoimmunity and hypercholesterolemia – the presence of high levels of cholesterol in the blood – by silencing a certain gene expression in mice. Gene expression is the process by which information from a gene [the unit of heredity in a living organism] is used.
Antigens – substances that provoke the production of auto-antibodies and elicit autoimmune responses in mice – were identified using a proteomic approach [the study of the structure and function of proteins]. Each antibody binds to a specific antigen by way of an interaction similar to the fit between a lock and a key.
Collaborative research project
“Marie Curie Actions funding helped me to bring together collaborative efforts from scientists from the US and Europe to conduct research into cardiovascular disease, which is a major threat to public health worldwide,” acknowledges Dr Merched. “At the personal level, the Marie Curie Action Fellowship [giving researchers the chance to gain experience abroad and in the private sector] helped to push my international career through strong collaboration, networking and a great deal of exposure to what is happening in the scientific arena.”
The discoveries made by the Atheromoto project are likely to help scientists gain a better understanding of how inflammation contributes to the build-up of plaques on arterial vascular walls. “The findings will undoubtedly fuel scientific debate concerning the origins of these diseases and widen the panel of therapeutic measures we might potentially undertake,” concludes Dr Merched.