Atherosclerosis is the most common cause of cardiovascular disease and is accompanied by high mortality rates and a poor prognosis. Semaphorin 7A (Sema7A) and its receptor β1 integrin have been reported to participate in the development of atherosclerosis. However, the role of Sema7A and β1 integrin in endothelial cell injury and endothelial-to-mesenchymal transition (EMT) in atherosclerosis remains undetermined, to the best of our knowledge. The mRNA and protein expression levels of Sema7A and β1 integrin in HUVECs were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and western blot analyses, respectively. HUVECs were induced with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) to establish an atherosclerosis cell model. Cell viability was measured using Cell Counting Kit-8 assay and the production of IL-1β, IL-6 and C-C motif chemokine ligand 2 was determined using ELISA. The expression levels of cell adhesion factors, intracellular adhesion molecule-1 and vascular cell adhesion molecule-1 were analyzed using RT-qPCR and western blot analyses. Cell apoptosis was detected using flow cytometry and western blotting. The levels of EMT-related markers were evaluated using RT-qPCR, western blotting and immunofluorescence staining. The results of the present study revealed that the expression levels of Sema7A and β1 integrin were significantly upregulated in ox-LDL-treated HUVECs. Treatment with ox-LDL significantly decreased cell viability, and increased the levels of inflammatory and adhesion factors, the cell apoptotic rate and the expression levels of EMT-related proteins. Knockdown of Sema7A reversed the ox-LDL-induced inflammatory responses and EMT, while the overexpression of β1 integrin reversed the Sema7A-mediated inhibitory effects on ox-LDL-treated HUVECs. In conclusion, the findings of the present study indicated that Sema7A and β1 integrin may play significant roles in atherosclerosis by mediating endothelial cell injury and EMT progression.

Septin 4 is a member of a family of GTP-binding proteins that has been previously reported regulate cytoskeletal organization. In addition, it has been suggested to serve a role in atherosclerosis. Therefore, the present study aimed to investigate the effects of Septin 4 on foam cell formation. THP-1 cells were first exposed to phorbol-12-myristate-13-acetate for differentiation into macrophages before being transformed into foam cells by treatment with oxidized low-density lipoprotein (ox-LDL). Septin 4 expression was then knocked down or overexpressed in THP-1 cells using transfection, whilst peroxisome proliferator activated receptor γ (PPARγ) was also inhibited using its selective antagonist (T0070907) in the presence of Septin 4 overexpression. Oil red staining was used to detect lipid uptake, and total cholesterol (TC), free cholesterol (FC) and ATP binding cassette subfamily A/G member 1 (ABCA1/G1) protein expression were also measured. The results demonstrated that upon ox-LDL stimulation, macrophages that were derived from THP-1 cells transformed into foam cells, where Septin 4 was highly expressed in ox-LDL-induced foam cells. Septin 4 knockdown promoted TC and FC levels, but reduced ABCA1/G1 protein expression. The protein expression levels of PPARγ and liver X receptor α (LXRα) were also decreased after Septin 4 knockdown. However, Septin 4 overexpression resulted in the opposite results being observed. Additionally, blocking PPARγ activity using its inhibitor T0070907 or knocking down LXRα expression using short hairpin RNA reversed the effects of Septin 4 overexpression on foam cell formation and cholesterol handling. In conclusion, Septin 4 may serve an important role in preventing foam cell formation by activating PPARγ/LXRα signaling and subsequently enhancing ABCA1/G1 expression.