Moderate dose alcohol protects against serum amyloid protein A1-induced endothelial dysfunction via both notch-dependent and notch-independent pathways.
Moderate dose alcohol protects against serum amyloid protein A1-induced endothelial dysfunction via both notch-dependent and notch-independent pathways.
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DOI：
10.1111/acer.14706
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Redmond EM
中科院分区：
文献类型：
--
作者：
Rajendran NK;Liu W;Chu CC;Cahill PA;Redmond EM
动脉内皮对于维持血管稳态和预防动脉粥样硬化性心血管疾病（CVD）至关重要。低至中度饮酒与减少动脉粥样硬化有关，并刺激内皮细胞中的 Notch 信号传导。我们研究的目的是确定酒精 (EtOH) 是否可以保护内皮免受血清淀粉样蛋白 A1 (SAA1) 诱导的激活/损伤，并确定这种保护是否完全依赖于 Notch。在存在或不存在 EtOH (25 mM)、Notch 配体 DLL4 (3 μg/ml) 或 Notch 抑制剂 DAPT (20 μM) 的情况下，对人冠状动脉内皮细胞 (HCAEC) 进行+/-“促动脉粥样硬化”SAA1 (1 μM) 刺激。从 Notch 受体和 hrt 靶基因表达增加可以看出，EtOH 刺激了 HCAEC 中的 Notch 信号传导。单独使用 EtOH 治疗或通过 DLL4 刺激 Notch 信号传导，可增加 eNOS 活性，并通过跨内皮电阻评估增强 HCAEC 屏障功能。此外，EtOH和DLL4均抑制SAA1诱导的单层渗漏、细胞粘附分子（ICAM、VCAM）表达和单核细胞粘附。 EtOH 的这些作用是 Notch 依赖性的，因为它们被 DAPT 和 Notch 受体（N1、N4）敲低所阻断。相比之下，EtOH 对 SAA1 诱导的炎症细胞因子（IL-6、IFN-γ）和活性氧（ROS）的抑制与 Notch 无关，因为这些作用不受 DAPT 或 N1 和/或 N4 敲低的影响。适量的酒精可通过Notch依赖性和Notch非依赖性机制防止SAA1诱导的内皮激活。在非激活状态下通过酒精维持内皮细胞有望保持血管稳态并防止动脉粥样硬化的发展。
Arterial endothelium is critical in maintaining vessel homeostasis and preventing atherosclerotic cardiovascular disease (CVD). Low-to-moderate alcohol consumption is associated with reduced atherosclerosis and stimulates Notch signaling in endothelial cells. The aim of our study was to determine whether alcohol (EtOH) protects the endothelium against serum amyloid A1 (SAA1)-induced activation/injury, and to determine whether or not this protection is exclusively Notch-dependent. Human coronary artery endothelial cells (HCAEC) were stimulated +/− ‘pro-atherogenic’ SAA1 (1 μM) in the absence or presence of EtOH (25 mM), the Notch ligand DLL4 (3 μg/ml), or the Notch inhibitor DAPT (20 μM). EtOH stimulated Notch signaling in HCAEC as seen by increased Notch receptor and hrt target gene expression. Treatment with EtOH alone, or stimulation of Notch signaling by DLL4, increased eNOS activity and enhanced HCAEC barrier function assessed by trans-endothelial electrical resistance. Moreover, EtOH and DLL4 both inhibited SAA1-induced monolayer leakiness, cell adhesion molecule (ICAM, VCAM) expression, and monocyte adhesion. These effects of EtOH were Notch-dependent as they were blocked with DAPT and by Notch receptor (N1, N4) knockdown. In contrast, EtOH’s inhibition of SAA1-induced inflammatory cytokines (IL-6, IFN-γ) and reactive oxygen species (ROS) were Notch-independent as these effects were unaffected by DAPT or by N1 and/or N4 knockdown. Alcohol at moderate levels protects against SAA1-induced endothelial activation via both Notch-dependent and Notch-independent mechanisms. Maintenance of endothelium by alcohol in a non-activated state would be expected to preserve vessel homeostasis and protect against atherosclerosis development.
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影响因子：
4.4
作者：
Briot A;Bouloumié A;Iruela-Arispe ML
通讯作者：
Iruela-Arispe ML
DOI：
10.1161/atvbaha.110.215681
发表时间：
2010-12
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Morrow D;Cullen JP;Liu W;Cahill PA;Redmond EM
通讯作者：
Redmond EM
影响因子：
3.1
作者：
Gkaliagkousi, Eugenia;Ferro, Albert
通讯作者：
Ferro, Albert
DOI：
10.1111/acer.13499
发表时间：
2017-12
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Fitzpatrick E;Han X;Liu W;Corcoran E;Burtenshaw D;Morrow D;Helt JC;Cahill PA;Redmond EM
通讯作者：
Redmond EM
DOI：
10.1111/acer.14415
发表时间：
2020-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Liu W;Harman S;DiLuca M;Burtenshaw D;Corcoran E;Cahill PA;Redmond EM
通讯作者：
Redmond EM