Work Package 2: P4 medicine for carotid stenosis and stroke

The most common cause of a stroke is a narrowing (obliteration) of one or both carotid arteries. This narrowing is caused by the progression of atherosclerotic plaques, which can rupture when they have reached a certain size. Strokes are currently the second leading cause of death worldwide; approx. 260,000 strokes are registered in Germany every year. In addition, physical and mental disabilities suffered from a stroke are a serious burden for patients, causing high healthcare costs.

The Department of Vascular and Endovascular Surgery of the TUM has one of the world's largest biobanks, which is unique due to its histological preparation. Based on a highly standardized preparation method developed over many years, histological samples are extracted from the carotid artery and then characterized by morphological attributes. In addition, all clinical parameters are collected in a database and can thus be taken into account in the analysis. Specifically, up to 1,250 patients during an endarterectomy, in which the obliterating plaques are removed from the carotid artery, had their histologically standardized preparations examined for their biological phenotype and stored in liquid nitrogen for further genomic and proteomic analysis. Preliminary experiments with this material have shown that the preparations are outstandingly suitable for this type of analysis, and that promising results can be obtained on the cause of a plaque rupture. In this way it is possible to correlate the clinical events with the genome, transcriptome and proteome data from the sample. The overarching goal of this investigation is to identify components of the vascular wall that are associated with a prognostically favorable or unfavorable event. The genetic studies also allow the identification of a causality of the proteins and functional networks involved. This not only enables better predictions of the likelihood of occurrence, but also new approaches to personalized prevention in the treatment of strokes.

Prof. Dichgans (Institute for Stroke and Dementia Research at LMU) and his research group play a leading role in the identification of risk genes and new RNA- or protein-based biomarkers for stroke, as well as in the identification of prognostic markers, which were shown associated with progression and predictability of cognitive impairments after strokes examined over a period of up to five years. In addition, the clinic coordinates several imaging studies including a study on carotid stenosis with ultra-high-resolution plaque MRI, which will help to determine and predict more precisely the individual progression and the rupture risk of vulnerable atherosclerotic plaques and microvascular changes.
A primary goal of WP2 is to link the results of the parallel biobank projects at the Klinikum rechts der Isar and the clinical examinations at the University of Munich. For example, markers that are identified in the multi-omics analysis of the vascular preparations are to be examined in more detail in the follow-up studies and, conversely, multi-omics data on prospective stroke cohorts in the tissue samples of the biobank are characterized. This synergy of the human biobank and clinical studies, as well as the existing experimental platforms at both clinics, will make it possible to identify not only new markers, but also new therapeutic goals in stroke prevention and therapy.

(updated: Dec. 2019)