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The role of non-coding RNAs in vascular disease

Non-coding RNAs (ncRNAs) are ribonucleic acid sequences “not coding” for proteins. Only DNA transcription takes place, the ncRNA is however further processed as mRNA.

The state-of-the-art “next-generation sequencing” revealed that 70 – 80% of the entire genome is translated into RNA, but less than 2% are coding for proteins [Leeper 2018]. These ncRNAs were first thought as “junk-RNA”. Further analyses showed however that they possess important regulatory functions in different cellular processes and development. Dependent upon their length, they can be divided in: (1) small non-coding microRNAs (miRNAs) (<200 bp) and (2) long non-coding RNAs (lncRNAs) (<200 bp), including circular RNAs (circRNAs).

Our results and also of other researchers demonstrated significant differences in the expression of miRNAs in different stages of atherosclerosis, cardiomyopathies and aneurysm, involved in apoptotic signalling pathways of smooth muscle and endothelial cells, neovascularization, inflammation and other pathophysiological changes within the vessel wall [Xu 2019, Yin 2019, Li 2018, Xu 2018, Jin 2018, Eken 2017].

Furthermore, ncRNAs are not only regulatory elements but are also involved in the regulation of hetero- and euchromatin and thus in epigenetics. MiRNAs and lncRNAs regulate DNA and histone methylation, expression of methyl- and acetyltransferases [Frías-Lasserre 2017]. In this way, ncRNAs and epigenetics work closely together.

Figure. Non-coding RNA H19 overexpressed in abdominal aortic aneurysm (AAA).
Figure. Non-coding RNA H19 overexpressed in abdominal aortic aneurysm (AAA). (a) Aortic tissue was collected from two AAA models: (i) ApoE−/− mice using Angiotensin II (AngII); (ii) porcine pancreatic elastase (PPE)-induced AAA was performed in C57BL/6J mice. (b) Volcano plot of deregulated transcripts in the AngII- AAA model. (d) Relative diameter of aortas at baseline, and after 7, 14 and 28 days post-aneurysm induction. In vivo knockdown of H19 was performed by utilizing site-specific antisense oligonucleotides (LNA-GapmeRs, H19 KD) or scrambled oligo controls [Li 2018].