Low shear stress (LSS) occurs in areas where atherosclerosis is prevalent. Many studies have revealed that signal transducer and activator of transcription 1 (STAT1) plays a significant role in cardiovascular disease. Nonetheless, the mechanism underlying the connection between STAT1 and LSS is not fully understood. The purpose of this study was to investigate the link between LSS and STAT1 in endothelial cells (ECs). Monolayer endothelial cells were stimulated or not stimulated by LSS. Protein expression and phosphorylation levels were determined by western blotting. Immunofluorescence was used to compare the protein expression differences in bifurcated and non-bifurcated human coronary arteries. Endothelial function was assessed by using a dihydroethidium assay, real-time PCR, western blotting and nitric oxide (NO)-sensitive fluorophore. Results showed that STAT1 played a key role in LSS-induced endothelium damage. Firstly, LSS activated STAT1, as evidenced by LSS-induced STAT1 (Tyr701) phosphorylation in ECs in vitro and the increased intimal STAT1 expression at bifurcation of human coronary arteries. Secondly, LSS-induced STAT1 phosphorylation was positively regulated by inhibitor of nuclear factor kappa-B kinase ε (IKKε). Additionally, LSS-promoted inflammatory factor expression was markedly reversed by silencing STAT1 (siSTAT1). LSS also increased reactive oxygen species (ROS) level and decreased endogenous NO release: however, siSTAT1 reversed these adverse effects through upregulating the antioxidant gene heme oxygenase-1(HO-1) and downregulating endothelial nitric oxide synthase (eNOS) Thr495 phosphorylation. According to our results, LSS-mediated EC injury may be associated with the activation of STAT1. Strategies designed to reduce STAT1 expression or inhibit STAT1 activation may be effective approaches for reducing the incidence of atherosclerosis.

中文翻译：

---

低剪切应力通过内皮细胞（ECs）中的STAT1破坏内皮功能。

低剪切应力（LSS）发生在动脉粥样硬化普遍的地区。许多研究表明，信号转导和转录激活因子1（STAT1）在心血管疾病中起重要作用。但是，尚未完全了解STAT1和LSS之间连接的基础机制。这项研究的目的是调查内皮细胞（ECs）中LSS和STAT1之间的联系。LSS刺激或不刺激单层内皮细胞​​。蛋白表达和磷酸化水平通过蛋白质印迹法确定。免疫荧光被用来比较人叉状动脉和非人叉状动脉中蛋白质表达的差异。内皮功能通过使用二氢乙锭测定，实时PCR，蛋白质印迹和一氧化氮（NO）敏感的荧光团进行评估。结果表明，STAT1在LSS诱导的内皮损伤中起关键作用。首先，LSS激活STAT1，这在体外培养的ECs中由LSS诱导的STAT1（Tyr701）磷酸化和人冠状动脉分叉处的内膜STAT1表达增加证明。其次，LSS诱导的STAT1磷酸化受到核因子κB激酶ε（IKKε）抑制剂的正调控。此外，沉默STAT1（siSTAT1）可显着逆转LSS促进的炎症因子表达。LSS还增加了活性氧（ROS）水平并减少了内源性NO释放：但是，siSTAT1通过上调抗氧化剂基因血红素加氧酶-1（HO-1）和下调内皮型一氧化氮合酶（eNOS）Thr495磷酸化来逆转这些不利影响。根据我们的结果，LSS介导的EC损伤可能与STAT1的激活有关。旨在减少STAT1表达或抑制STAT1活化的策略可能是减少动脉粥样硬化发生率的有效方法。