Proteogenomic discovery of endothelium-derived microproteins in cardiovascular disease

The expression of these miPs is profoundly altered by endothelial cell activation in vitro and in a mouse model of endothelial dysfunction and atherogenesis. Since endothelial miPs represent an entirely novel class of signalling molecules, whether alterations in the expression of miPs contribute to the development of human cardiovascular disease (CVD) or whether miPs could be used as novel biomarkers is not known. We hypothesize that miPs play an important role in the dysregulation of endothelial cell function in CVD. Therefore, this project aims to identify miPs in blood vessels and in the circulation of patients with CVD. To accomplish this, we will apply a proteogenomic approach comprising genomic, proteomic and bioinformatic analyses to determine alterations in the expression of smORF-encoded miPs in samples from patients suffering from arterial hypertension, coronary artery disease, acute myocardial infarction, aortic aneurysm and diabetes mellitus compared to age-matched individuals not suffering from those conditions. With our approach, we expect to identify novel endothelium-derived miPs, and detect their presence in the bloodstream to assess their relevance in CVD. The results of such an investigation are expected to open the way to the identification of new communication pathways between cells and organs. Also because of their small size, miPs should be ideal to target in novel therapeutic approaches.

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