The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study

Abstract

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood and only partially characterized. AAA are also complicated in case of bicuspid aorta valve (BAV) anatomy. There is emerging evidence about the crucial role of endothelium-related pathways, which show in AAA an altered expression and function. Here, we examined the involvement of ERG-related pathways in the differential progression of disease in aortic tissues from patients having a BAV or tricuspid aorta valve (TAV) with or without AAA. Our findings identified ERG as a novel endothelial-specific regulator of TGF-β-SMAD, Notch, and NO pathways, by modulating a differential fibrotic or calcified AAA progression in BAV and TAV aortas. We provided evidence that calcification is correlated to different ERG expression (as gene and protein), which appears to be under control of Notch signaling. The latter, when increased, associated with an early calcification in aortas with BAV valve and aneurysmatic, was demonstrated to favor the progression versus severe complications, i.e., dissection or rupture. In TAV aneurysmatic aortas, ERG appeared to modulate fibrosis. Therefore, we proposed that ERG may represent a sensitive tissue biomarker to monitor AAA progression and a target to develop therapeutic strategies and influence surgical procedures.

Neuroinflammation and Neurodegenerative Diseases: How Much Do We Still Not Know?

“…The latter offers the possibility of hypothesizing and developing new treatments and identifying diagnostic and prognostic biomarker profiles for neuroinflammation and ND. They could include the assessment of transmigration and activation levels of monocytes, as well as the levels, activation, and quantification of clonotypic cells and their mediators, and the evaluation of expression of NF-kB and other transcriptional factors (i.e., ERG factor) and the related pathways [146,147]. The concomitant assessment of microRNAs and epigenetic factors involved in the regulation of these mechanisms could be additionally helpful.…”