ATHEROREMO

European Collaborative Project on Inflamation and Vascular Wall Remodelling in Atherosclerosis

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 Obiettivo del progetto (Objective)

'The health of the EC population has never been better. However, serious public health problems remain, which cannot be ignored including high levels of premature death due to cardiovascular diseases. Thus, new preventive, diagnostic and therapeutic strategies against atherosclerotic cardiovascular diseases are needed. The atherosclerotic changes of the vascular wall are central in the development of cardiovascular complications. The traditional view that atherosclerosis is simply a lipid storage disease has recently been challenged by evidence that inflammation plays a central role in all stages of atherosclerosis. However, molecular mechanisms linking inflammation to atherosclerosis development are not fully understood, and this has severely hampered the advance of diagnostic and therapeutic programs. AtheroRemo aims to identify novel inflammatory mechanisms in vascular remodelling by combining the exploration of human biobanks with animal models and established cellular models. This new knowledge will be used to develop new preventive, diagnostic and therapeutic strategies against atherosclerotic cardiovascular disease. AtheroRemo contains several unique strengths: 1) Outstanding expertise on immunity and inflammation. Our expertise facilitates the breakthroughs in the immuno-inflammatory targeted vascular treatments. 2) Finest European cohorts to search for molecular mechanisms behind atherosclerosis development allowing us to combine underlying genetics with lipidomic profiles in multiple cohorts in order to obtain risk factors and biomarker panel related to inflammatory remodelling. 3) Accelerated target validation with novel liposomal-targeted delivery of nucleic acid-based therapeutics in appropriate animal models. Four SME partners able to exploit the new knowledge support AtheroRemo research. Thus, we expect to translate a number of novel findings into potential clinical applications such as new diagnostic tools (biomarkers) and therapeutics.'

Introduzione (Teaser)

Understanding how atherosclerotic plaques form would certainly help in the development of new therapies against cardiovascular disease. In this context, a large European consortium looked at the role of inflammation in atherosclerosis development.

Descrizione progetto (Article)

The main cause of cardiovascular disease is the formation of atherosclerotic plaques on vascular walls. Emerging data challenges the current belief that atherosclerosis is a lipid storage disease, and incriminates inflammation in its pathophysiology. However, our understanding of the mechanisms that link inflammation with atherosclerosis development is limited.

With EU funding, the 'European Collaborative Project on inflamation and vascular wall remodelling in atherosclerosis' (http://www.atheroremo.org/ (ATHEROREMO)) project investigated the role of inflammatory remodelling in atherosclerosis development. The project combined clinical studies with genomics and lipidomics high-throughput analyses, and basic research, thereby hoping to unveil novel molecular targets that could be exploited in diagnostics and treatment.

Alarmingly, researchers found a strong association between cardiovascular disease and dental infections as well as root canal treatment. Genomic analysis revealed that this was due to streptococcal bacteria.

With respect to the molecular mechanisms responsible for vascular wall remodelling, the consortium identified novel immune signalling events such as pattern recognition receptors and chemokines. They found that reduction of the chemokine levels prevented atherosclerosis, thereby indicating that preventing unwanted inflammation could serve as a therapeutic strategy. Alternative treatment strategies could entail the reversal of the gene expression changes in the arterial wall induced by atherosclerosis.

From a diagnostics perspective, the ATHEROREMO study identified novel imaging and lipidomic biomarkers that have a true potential to change current clinical risk evaluation strategies for patients. In addition, the levels of circulating ceramides were found to outperform cholesterol measurement with respect to identifying people at risk of cardiovascular disease. These observations also led to the development of new diagnostic kits.

Overall, the activities of the ATHEROREMO project greatly advance our understanding of the inflammatory events and mechanisms that lead to atherosclerosis and cardiovascular disease. In the long run, project findings are expected to improve the prognosis and diagnosis of high-risk individuals, as well as provide novel therapeutic modalities.