ATHEROREMO Consortium - targeting high risk atherosclerotic plaques

The atherosclerotic changes of the vascular wall are central in the development of serious cardiovascular complications. The traditional view that atherosclerosis is simply a lipid storage disease has recently been challenged by a growing body of evidence that immunity and inflammation play a central role in all stages of atherosclerotic disease from the early initial lesion to the late-stage plaque rupture. However, molecular mechanisms linking inflammation to premature atherosclerosis development are not fully understood, and this has severely hampered the advance of diagnostic and therapeutic programs.

It has been observed that atheromatous plaque development takes place within, rather than on, the arterial wall. Thus, vascular events often follow the rupture of previously less prominent plaques. Novel targets of plaque regression could include decrease of endothelial injury and lipid content as well as alteration of the inflammatory milieu in the vessel wall to decrease the susceptibility of plaque growth and rupture. Thus, AtheroRemo has been designed to advance the present knowledge on the role of inflammatory remodeling in the different stages of atherosclerosis.

AtheroRemo will identify and validate novel drug targets as well as devise and validate diagnostic tests. AtheroRemo will also provide important knowledge for the development of strategies for prevention and clinical management of vascular diseases.

The AtheroRemo consortium has a strong potential to achieve a significant number of scientific breakthroughs of high translational value due to several unique strengths:

• Clinical and clinico-pathological cohorts: AtheroRemo originality lies in the possibility to evaluate the genetic makeup of atherosclerosis during its different developmental stages in large population cohorts. Particularly noteworthy is the possibility to characterize atherosclerosis and remodelling processes in a unique clinico-pathological series and in an intravascular ultrasound (IVUS) study that has particularly been designed for AtheroRemo.
• Lipidomics: In addition to the latest genetic/genomic platforms AtheroRemo has access to automated high throughput lipidomics platforms. Combining large-scale genotyping data with world-class lipidomic profiling allows us to relate genetic risk factor scores to plasma biomarkers.
• Functional Genomics and Target Validation Platforms: Accelerated target validation by functional genomics will be done by using targeted liposomal delivery of nucleic acid-based therapeutics (e.g. antisense oligonucleotides and siRNAs) in appropriate cell and animal models.
• Immunology and Inflammation cluster: AtheroRemo basic science component includes groups with outstanding expertise and track-record on immunity and inflammation research in atherosclerosis.