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Endothelial long non-coding RNAs

Periodic Reporting for period 3 - Angiolnc (Endothelial long non-coding RNAs)

Reporting period: 2019-01-01 to 2020-06-30

Endothelial cells comprise the inner cellular cover of the vasculature and play central roles in pathophysiological processes of many diseases including cardiovascular diseases and cancer. More than 70 % of the human genome encodes for non-coding RNAs (ncRNAs) and increasing evidence suggests that a significant portion of these ncRNAs are functionally active as RNA molecules. Angiolnc aims to explore the function of long ncRNAs (lncRNAs) and particular circular RNAs (circRNAs) in the endothelium. LncRNAs comprise a heterogenic class of RNAs with a length of > 200 nucleotides and circRNAs are generated by back splicing. These ncRNAs may be useful as therapeutic targets or as biomarkers.
The work is done in the Dimmeler laboratory (http://www.cardiovascular-regeneration.com/)
During the first part of the funding period, we have identified and characterized several lncRNAs and one circRNA, which control endothelial cell functions. In addition, we have extended the project to determine lncRNAs in vessel maturation by assessing lncRNA control of pericytes, which are stabilizing newly formed capillaries. Ongoing studies are elucidating the in vivo function of selected candidates by using pharmacological and genetic strategies.
We also explored the regulation and potential use of lncRNAs as biomarkers in patients with coronary artery disease and report on one lncRNA, which is associated with atherosclerotic plaques in humans and determines prognosis.
With the present project first insights into the regulation and function of long non-coding RNAs in the vascular system could be obtained. Most importantly, our ongoing work describes a novel permeability control by a lncRNA as well as an in vivo phenotype induced by specific genetic deletion one circRNA. Both are entirely novel insights. With respect to the importance of non-coding RNAs in humans, we showed that the lncRNA MALAT1 is determining prognosis of patients with coronary artery disease. Our ongoing studies, using single cell sequencing technologies, will provide additional and likely important insights into the regulation of lncRNAs in a cell type specific manner in patient-derived samples.