Your browser doesn't support javascript.
loading
Macrophage KLF15 prevents foam cell formation and atherosclerosis via transcriptional suppression of OLR-1.
Song, Zheng-Kun; Zhao, Li; Liu, De-Shen; Zhao, Ling-Na; Peng, Qin-Bao; Li, Zi-Yao; Wu, Jia-Yong; Chen, Si-Kai; Huang, Fang-Ze; Chen, Xing; Lin, Tian-Xiao; Guan, Li; Meng, Wei-Peng; Guo, Jia-Wei; Su, Yue-Nian; He, Xiao-Xia; Liang, Si-Jia; Zhu, Peng; Zheng, Shao-Yi; Du, Song-Lin; Liu, Xiu.
Afiliación
  • Song ZK; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Zhao L; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Liu DS; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Zhao LN; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Peng QB; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Li ZY; Department of Thoracic Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830000, China.
  • Wu JY; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Chen SK; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Huang FZ; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Chen X; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Lin TX; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Guan L; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Meng WP; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Guo JW; Department of Pharmacology, School of Medicine, Yangtze University, Jingzhou 434023, China.
  • Su YN; Department of Rehabilitation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • He XX; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Liang SJ; Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • Zhu P; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Zheng SY; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: zhsy@smu.edu.cn.
  • Du SL; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: dsl@smu.edu.cn.
  • Liu X; Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: liux266@smu.edu.cn.
J Mol Cell Cardiol ; 186: 57-70, 2024 01.
Article en En | MEDLINE | ID: mdl-37984156
BACKGROUND: Macrophage-derived foam cells are a hallmark of atherosclerosis. Scavenger receptors, including lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (OLR-1), are the principal receptors responsible for the uptake and modification of LDL, facilitating macrophage lipid load and the uptake of oxidized LDL by arterial wall cells. Krüppel-like factor 15 (KLF15) is a transcription factor that regulates the expression of genes by binding to the promoter during transcription. Therefore, this study aimed to investigate the precise role of macrophage KLF15 in atherogenesis. METHODS: We used two murine models of atherosclerosis: mice injected with an adeno-associated virus (AAV) encoding the Asp374-to-Tyr mutant version of human PCSK9, followed by 12 weeks on a high-fat diet (HFD), and ApoE-/-- mice on a HFD. We subsequently injected mice with AAV-KLF15 and AAV-LacZ to assess the role of KLF15 in the development of atherosclerosis in vivo. Oil Red O, H&E, and Masson's trichome staining were used to evaluate atherosclerotic lesions. Western blots and RT-qPCR were used to assess protein and mRNA levels, respectively. RESULTS: We determined that KLF15 expression was downregulated during atherosclerosis formation, and KLF15 overexpression prevented atherosclerosis progression. KLF15 expression levels did not affect body weight or serum lipid levels in mice. However, KLF15 overexpression in macrophages prevented foam cell formation by reducing OLR-1-meditated lipid uptake. KLF15 directly targeted and transcriptionally downregulated OLR-1 levels. Restoration of OLR-1 reversed the beneficial effects of KLF15 in atherosclerosis. CONCLUSION: Macrophage KLF15 transcriptionally downregulated OLR-1 expression to reduce lipid uptake, thereby preventing foam cell formation and atherosclerosis. Thus, our results suggest that KLF15 is a potential therapeutic target for atherosclerosis.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Células Espumosas Límite: Animals / Humans Idioma: En Revista: J Mol Cell Cardiol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aterosclerosis / Células Espumosas Límite: Animals / Humans Idioma: En Revista: J Mol Cell Cardiol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido