IRF-1 contributes to the pathological phenotype of VSMCs during atherogenesis by increasing CCL19 transcription

• Published in: Aging (Albany, NY.) Vol. 13; no. 1; pp. 933 - 943
• Main Authors: Shen, Yongbin, Sun, Zhanfeng, Mao, Shuran, Zhang, Yingnan, Jiang, Weiliang, Wang, Haitao
• Format: Journal Article
• Language: English
• Published: United States Impact Journals 15.01.2021
• Subjects: Aged; Animals; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Becaplermin - pharmacology; Cell Movement - drug effects; Cell Movement - genetics; Cell Proliferation - drug effects; Cell Proliferation - genetics; Chemokine CCL19 - genetics; Chemokine CCL19 - metabolism; Extracellular Matrix - metabolism; Female; Gene Knockdown Techniques; Humans; Inflammation - genetics; Inflammation - metabolism; Interferon Regulatory Factor-1 - genetics; Interferon Regulatory Factor-1 - metabolism; Male; Mice; Mice, Knockout, ApoE; Middle Aged; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Research Paper; atherosclerosis; VSMCS; IRF-1; CCL19
• ISSN: 1945-4589; 1945-4589
• DOI: 10.18632/aging.202204

Atherosclerosis (AS) is a chronic inflammatory disease that mainly involves the large and middle arteries, but the specific mechanism is not precise. Chemokine ligand 19 (CCL19) has been reported highly expressed in peripheral blood of patients with atherosclerosis, but its role lacks explicit data. By ELISA assay and immunohistochemical (IHC) analysis, we found that the CCL19 was significantly up-regulated in AS. Therefore, we tried to clarify whether CCL19 expression was related to the progression of AS. QRT-PCR and western blot demonstrated that overexpression of CCL19 promoted the secretion of inflammatory factors and the deposition of the extracellular matrix, and facilitated the proliferation and migration of VSMCS. Besides, knockdown of CCL19 reduced the inflammation, collagen secretion, proliferation and migration of VSMCS induced by PGDF-BB. The results of database analysis, chromatin immunoprecipitation (ChIP) and luciferase assay showed that interferon regulatory factor 1 (IRF-1) activated the expression of CCL19 at the transcriptional level. Importantly, silencing IRF-1 inhibited atherosclerosis in high-fat-fed mice, inhibited the proliferation and migration of VSMCS, and down-regulated the expression of CCL19. Summing up, the results demonstrated that IRF-1 contributed to the pathological phenotype of VSMCs during atherogenesis by increasing CCL19 transcription.