The sympathetic transmitter norepinephrine inhibits VSMC proliferation induced by TGFβ by suppressing the�expression of the TGFβ receptor ALK5 in aorta remodeling

Abstract

The sympathetic system is involved in the arterial diseases, but its mechanism remains poorly understood. The present study aimed to explore the impact of the sympathetic neurotransmitter norepinephrine (ne) on transforming growth factor (TGF) β signaling and the role of ne in aortic remodeling. Guanethidine was used to induce a regional chemical sympathetic denervation (cSd) in angiotensin ii (angii) and β-aminopropionitrile (BaPn)-induced aortic aneurysm models. The diameter of the aorta was measured, and elastic fiber staining was performed. TGFβ type i receptor kinase (alK5) expression in rat aortic ne-treated vascular smooth muscle cells (VSMcs) was detected by reverse transcription-quantitative Pcr and western blotting. The effects of ne and alK5 overexpression on migration, proliferation, apoptosis and TGFβ signaling were also evaluated. Furthermore, adrenergic receptor blockers were used to determine which receptor was involved in the modulation on TGFβ signaling by ne. The results of the present study demonstrated that cSd protected rats from angii+BaPn-induced aortic remodeling and aneurysm formation. compared with the control group, ne inhibited VSMc proliferation and migration, but promoted apoptosis by suppressing alK5 expression, reversing the effects of TGFβ signaling through the suppression of the SMad-dependent canonical pathway and promotion of the non-canonical pathway. These effects were prevented by alK5 overexpression. The inhibition of α-or β-adrenergic receptors alleviated the ne-mediated suppression of alK5 expression. in conclusion, regional cSd protected rats from aortic aneurysm. ne inhibited SMad2/3-dependent TGFβ signaling by suppressing alK5 expression, which may serve an important role in VSMc biological functions. Both α-and β-adrenergic receptors were involved in the regulation of alK5 expression by ne. abnormal sympathetic innervation of the aorta may be used as a therapeutic target in aortic diseases.

Effects of Massage on Neuro-Vascular Regulation and Apoptosis in Rabbits with Cervical Spondylosis of the Vertebral Artery Type

“…NE is a well-known vasoconstrictor, an important neurotransmitter secreted by sympathetic nerves, which can affect some arterial diseases by inhibiting the proliferation of vascular smooth muscle cells (VSMCs) [21,22]. It has been shown that stimulation of the cervical sympathetic ganglia could increase NE levels and decrease basilar artery (BA) blood supply, whereas adrenergic receptor blockade could inhibit this effect [4].…”

Targeting Tyrosine Hydroxylase for Abdominal Aortic Aneurysm: Impact on Inflammation, Oxidative Stress, and Vascular Remodeling

“…5 Furthermore, Ang II, a key player in AAA formation, 26 enhances sympathetic activity inducing aortic MMP2, which plays a critical role in the onset and progression of several aortopathies including AAA. 27 Moreover, Hu et al 6 showed that catecholamines regulate TGF (transforming growth factor)-β signaling in aortic aneurysms, limiting VSMC proliferation and fostering apoptosis, thereby modulating vascular remodeling. Interestingly, the TH pathway has been previously documented in the vascular wall, and TH expression has been demonstrated in VSMC, endothelial cells, and regulatory T cells.…”

“…In fact, human aortic dissection is frequently associated with an increase in sympathetic activity, 5 while local sympathetic denervation ameliorates experimental aneurysms. 6 Recently, using a new mouse model that overexpresses the NOR-1 (neuron-derived orphan receptor-1) in the vascular wall 7 and recapitulates key aspects of human AAA, we suggested the upregulation of genes associated to sympathetic activity in aneurysmal aorta. 8 They include key components of the tyrosine hydroxylase (TH) pathway involved in the biosynthesis of catecholamines, important hormones and neurotransmitters in both the central and peripheral nervous systems.…”

rno-miR-128-3p promotes apoptosis in rat granulosa cells (GCs) induced by norepinephrine through Wilms tumor 1 (WT1)

“…NE also promotes follicle development (Mayerhofer 1997 ; Doganay 2010 ). Furthermore, it is revealed that NE represses VSMC proliferation through repressing ALK5 expression (Hu 2020 ). NE also diminishes dopaminergic cell apoptosis induced by 6-hydroxydopamine (Zhu 2019 ).…”