Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 30 July 2022 / Approved: 2 August 2022 / Online: 2 August 2022 (03:43:22 CEST)

How to cite: Pisano, C.; Balistreri, C.R.; Terriaca, S.; Scioli, M.G.; Nardi, P.; Orlandi, A.; Ruvolo, G. The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study. Preprints 2022, 2022080030 (doi: 10.20944/preprints202208.0030.v1). Pisano, C.; Balistreri, C.R.; Terriaca, S.; Scioli, M.G.; Nardi, P.; Orlandi, A.; Ruvolo, G. The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study. Preprints 2022, 2022080030 (doi: 10.20944/preprints202208.0030.v1).

Abstract

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.

Keywords

ascending aorta aneurysm; bicuspid aorta valve; tricuspid aorta valve; ERG transcriptional factor pathway; TGF-β-SMAD, Notch, and NO pathways modulation.

Subject

MEDICINE & PHARMACOLOGY, Cardiology

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