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.
摘要：
升主动脉动脉瘤（AAA）的发病和进展的病理生物学尚未得到很好的理解，仅有部分特征。AAA在二叶主动脉瓣(BAV)解剖结构的情况下也是复杂的。有新的证据表明内皮相关通路的关键作用，在AAA中显示了改变的表达和功能。这里,我们研究了有BAV或三尖瓣主动脉瓣(TAV)伴或不伴AAA的患者主动脉组织中ERG相关通路参与疾病的不同进展.我们的发现将ERG确定为TGF-β-SMAD的新型内皮特异性调节因子，缺口,和NO途径，通过调节BAV和TAV主动脉的不同纤维化或钙化AAA进展。我们提供的证据表明钙化与不同的ERG表达（作为基因和蛋白质），这似乎是在Notch信号的控制之下。后者,当增加时，与BAV瓣膜和动脉瘤的主动脉早期钙化有关，被证明有利于进展而不是严重的并发症，即，解剖或破裂。在TAV动脉瘤主动脉中，ERG似乎调节纤维化。因此,我们提出,ERG可能是监测AAA进展的敏感组织生物标志物,也是制定治疗策略和影响外科手术的目标.
