LIM Homeobox 2 Increases Adhesion-Regulating Molecule 1 Transcription to Facilitate the Pathological Progression of Oxidized Low-Density Lipoprotein-Stimulated Atherosclerotic Cell Models

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.