Deletion of large-conductance calcium-activated potassium channels promotes vascular remodelling through the CTRP7-mediated PI3K/Akt signaling pathway.
Deletion of large-conductance calcium-activated potassium channels promotes vascular remodelling through the CTRP7-mediated PI3K/Akt signaling pathway.
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大电导钙激活钾通道的缺失通过 CTRP7 介导的 PI3K/Akt 信号通路促进血管重塑
DOI：
10.3724/abbs.2022179
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发表时间：
2022-12-25
影响因子：
3.7
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Bi J;Duan Y;Wang M;He C;Li X;Zhang X;Tao Y;Du Y;Liu H
大电导钙激活钾（BK）通道是血管张力和结构的关键调节剂和潜在的治疗靶点，并且该通道的异常表达或功能障碍与许多血管疾病有关。血管重构是严重血管疾病的早期病理基础。延缓血管重构的进展可以减少心血管事件，但其发病机制尚不清楚。为了阐明BK通道在血管重构中的作用，我们使用BK通道α亚基敲除（BK α <$/<$）大鼠。结果表明，BK α β/β大鼠与WT大鼠相比，主动脉内径和外径变小，壁增厚，纤维化增加，弹性纤维紊乱。当人脐动脉平滑肌细胞（HUASMCs）中BK α的表达和功能受到抑制时，基质金属蛋白酶2（MMP 2）、MMP 9和白细胞介素6（IL-6）的表达增强，而平滑肌细胞收缩表型蛋白的表达减少。RNA测序、生物信息学分析和qPCR验证表明C1 q/肿瘤坏死因子相关蛋白7（CTRP 7）为下游靶基因。此外，在CTRP 7敲低后，观察到除了MMPs的表达外，IL-6、平滑肌细胞收缩表型蛋白的表达趋势相似。此外，在HUASMCs中敲低BK α和CTRP 7激活PI 3 K/Akt信号传导。此外，CTRP 7在血管平滑肌细胞（VSMC）中表达，BK α缺乏通过降低CTRP 7水平激活PI 3 K/Akt通路。因此，我们首先表明，BK通道缺陷导致血管重塑。BK通道和CTRP 7可能成为治疗心血管疾病的潜在靶点。
The large-conductance calcium-activated potassium (BK) channel is a critical regulator and potential therapeutic target of vascular tone and architecture, and abnormal expression or dysfunction of this channel is linked to many vascular diseases. Vascular remodelling is the early pathological basis of severe vascular diseases. Delaying the progression of vascular remodelling can reduce cardiovascular events, but the pathogenesis remains unclear. To clarify the role of BK channels in vascular remodelling, we use rats with BK channel α subunit knockout (BK α ‒/‒). The results show that BK α ‒/‒ rats have smaller inner and outer diameters, thickened aortic walls, increased fibrosis, and disordered elastic fibers of the aortas compared with WT rats. When the expression and function of BK α are inhibited in human umbilical arterial smooth muscle cells (HUASMCs), the expressions of matrix metalloproteinase 2 (MMP2), MMP9, and interleukin-6 are enhanced, while the expressions of smooth muscle cell contractile phenotype proteins are reduced. RNA sequencing, bioinformatics analysis and qPCR verification show that C1q/tumor necrosis factor-related protein 7 ( CTRP7) is the downstream target gene. Furthermore, except for that of MMPs, a similar pattern of IL-6, smooth muscle cell contractile phenotype proteins expression trend is observed after CTRP7 knockdown. Moreover, knockdown of both BK α and CTRP7 in HUASMCs activates PI3K/Akt signaling. Additionally, CTRP7 is expressed in vascular smooth muscle cells (VSMCs), and BK α deficiency activates the PI3K/Akt pathway by reducing CTRP7 level. Therefore, we first show that BK channel deficiency leads to vascular remodelling. The BK channel and CTRP7 may serve as potential targets for the treatment of cardiovascular diseases.
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影响因子：
4
作者：
Sancho M;Kyle BD
通讯作者：
Kyle BD
影响因子：
9.1
作者：
Mullington, Janet M.;Haack, Monika;Toth, Maria;Serrador, Jorge A.;Meier-Ewert, Hans K.
通讯作者：
Meier-Ewert, Hans K.
DOI：
10.1152/ajpendo.00344.2016
发表时间：
2017-04-01
影响因子：
5.1
作者：
Petersen, Pia S.;Lei, Xia;Wong, G. William
通讯作者：
Wong, G. William
影响因子：
20.1
作者：
Plüger, S;Faulhaber, J;Pongs, O
通讯作者：
Pongs, O
影响因子：
3.9
作者：
Tobal R;Potjewijd J;van Empel VPM;Ysermans R;Schurgers LJ;Reutelingsperger CP;Damoiseaux JGMC;van Paassen P
通讯作者：
van Paassen P