An international team of researchers, led by Lars Magedefessel from the DZHK partner site Munich, Experimental Vascular Medicine @ TUM, was able to show that lncRNA H19, from the novel class of long non-coding RNA molecules (>200 base pairs; lncRNA)) is an important regulator of vascular smooth muscle cell survival (VSMC) and hence inhibition decreases growth and progression of abdominal aortic aneurysm (AAA).
AAA is a dilation of the abdominal aorta eventually leading to rupture which can currently only be treated by surgical means such as endovascular aortic repair (EVAR) or open repair. No causal therapy preventing and no medical therapy abrogating AAA development is available. lncRNAs are thought to be of great therapeutic potential due to their superordinate and well conserved role in regulatory processes. VSMCs are a crucial cellular component in AAA pathogenesis and increased apoptosis has been shown at rupture sites. In their current study, the authors show that H19 is highly expressed in AAA in human and mice and in vivo silencing significantly limits aneurysm growth in two different murine models. In a dynamic cell culture experiment H19 inhibition significantly reduced VSMC apoptosis. Hypoxia inducible factor 1 (HIF1a) is known to be crucial in the hypoxic micromilieu of the aneurysmatic aortic wall and was identified as the main downstream effector of H19 affecting cell survival.
These findings have recently been published in Circulation and harbor future therapeutic potential by local endovascular RNA-therapy.