内皮-间质转化(EndMT)和内皮细胞凋亡已被证明在动脉粥样硬化(AS)进展中起作用。为了加深这方面的知识,在氧化低密度脂蛋白(ox-LDL)刺激的AS细胞模型中,我们研究了LIM同源盒2(LHX2)和黏附调节分子1(ADRM1)对EndMT和内皮细胞凋亡的影响.利用Ox-LDL处理人脐静脉内皮细胞(HUVECs),构建体外AS模型,然后测量LHX2和ADRM1表达。之后,在HUVEC中进行功能增益和功能丧失测定,然后检测细胞活力,入侵,迁移,和细胞凋亡和炎症因子的表达[肿瘤坏死因子(TNF)-α,白细胞介素(IL)-1β,和IL-6],EndMT相关蛋白[CD31,血管上皮(VE)-钙黏着蛋白,波形蛋白,α-平滑肌肌动蛋白(SMA),Snai1、Snai2和Twist1],和凋亡蛋白裂解的caspase-3。LHX2和ADRM1之间的相互作用用双荧光素酶报告基因和染色质免疫沉淀分析。在ox-LDL诱导的HUVEC中观察到高水平的LHX2和ADRM1。在ox-LDL治疗的HUVECs中,LHX2或ADRM1敲低可促进CD31和VE-钙粘蛋白水平,生存能力,入侵,和迁移,减少细胞凋亡和TNF-α的表达,IL-1β,IL-6波形蛋白,α-SMA,Snai1,Snai2,Twist1和裂开的半胱天冬酶-3。机械上,LHX2与ADRM1启动子结合以促进ADRM1转录。ADRM1的过表达消除了上述LHX2敲低对ox-LDL诱导的HUVECs的影响。LHX2通过增加ADRM1转录促进ox-LDL刺激的AS细胞模型的病理进展。
Endothelial-mesenchymal transition (EndMT) and endothelial cell apoptosis have been documented to have a role in atherosclerosis (AS) progression. To deepen knowledge in this aspect, our study investigated the effect of LIM homeobox 2 (LHX2) and adhesion-regulating molecule 1 (ADRM1) on EndMT and endothelial cell apoptosis in the oxidized low-density lipoprotein (ox-LDL) -stimulated AS cell model.Ox-LDL was utilized to treat human umbilical vein endothelial cells (HUVECs) for constructing an AS model in vitro, followed by measurement of LHX2 and ADRM1 expressions. Afterward, gain- and loss-of-function assays were performed in HUVECs, followed by detection of cell viability, invasion, migration, and apoptosis and the expression of inflammatory factors [tumor necrosis factor (TNF) -α, interleukin (IL) -1β, and IL-6], EndMT-related proteins [CD31, vascular epithelium (VE) -cadherin, vimentin, α-smooth muscle actin (SMA), Snai1, Snai2, and Twist1], and the apoptotic protein cleaved caspase-3. Interactions between LHX2 and ADRM1 were analyzed with dual-luciferase reporter gene and chromatin immunoprecipitation assays.High levels of LHX2 and ADRM1 were observed in ox-LDL-induced HUVECs. In ox-LDL-treated HUVECs, LHX2, or ADRM1 knockdown promoted CD31 and VE-cadherin levels, viability, invasion, and migration and reduced apoptosis and the expressions of TNF-α, IL-1β, IL-6, vimentin, α-SMA, Snai1, Snai2, Twist1, and cleaved caspase-3. Mechanistically, LHX2 bound to the ADRM1 promoter to promote ADRM1 transcription. Overexpression of ADRM1 annulled the aforementioned effects of LHX2 knockdown on ox-LDL-induced HUVECs.LHX2 facilitates the pathological progression of ox-LDL-stimulated AS cell models by increasing ADRM1 transcription.