ALK5介导新生交感神经调控TGF-β信号通路在主动脉夹层发病机制中的作用

主动脉夹层（Aortic dissection，AD）发病的重要基础是主动脉结构改变。动脉壁交感纤维丰富而静脉壁几乎没有交感纤维，我们前期专注交感支配对AD的影响，发现AD患者主动脉壁存在严重的交感神经新生(sympathetic sprouting)；交感神经化学消融术推迟大鼠模型AD形成和破裂，并显著调节TGF-β信号通路，尤其是TGF-β receptor1(ALK5)表达。ALK5突变致经典的遗传性主动脉瘤(Loeys–Dietz syndrome)，其突出的分子生物学特征是TGF-β通路由Canonical signaling优势向Non-canonical signaling优势逆转。由此我们提出AD发病机制的新设想：主动脉壁新生交感神经负向调节ALK5表达，逆转TGF-β信号通路优势，启动、促进主动脉壁结构重构并形成AD；ALK5是介导交感神经系统调节TGF-β通路的关键分子。

Aortic dissection is characterized by aorta wall remodeling. The sympathetic nerve innervation is rich in arteries but poor in veins. Our former research demonstrated a severe sympathetic sprouting in the aortic dissection patients aorta wall. We also demonstrated that chemical sympathectomy postpone aortic dissection formation and aorta rupture in rat model. Our Molecular Biology research revealed that chemical sympathectomy modulates TGF-β signaling，especially，down-regulates TGF-β receptor1(ALK5). ALK5 mutation results in a hereditary aortic aneurysm named Loeys–Dietz syndrome, which is characterized by a switch from Canonical TGF-β signaling dominance to a Noncanonical TGF-β signaling dominance. Therefore, we propose a new pathogenesis hypothesis for aortic dissection：Newly sprouted sympathetic nerves down-regulates ALK5 and reverse TGF-β signaling dominance，thus initiating and promoting aorta remodeling into aortic dissection. ALK5 is a key molecular mediates the impact of sympathetic nerve system on TGF-β signaling.