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Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model.
Liang, Ling; Song, Jing; Miao, Shisheng; Xie, Qiang; Li, Weihua; Huang, Honglang; Shen, Dongyan; Zhang, Wei.
Afiliação
  • Liang L; Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China. Electronic address: ravennaliang@sina.com.
  • Song J; Laboratory Animal Center, Xiamen University, Xiamen, 361005, China.
  • Miao S; Department of Cardiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, China.
  • Xie Q; Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China; Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First A
  • Li W; Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China; Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First A
  • Huang H; Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
  • Shen D; Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
  • Zhang W; Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China. Electronic address: zhangw@xmu.edu.cn.
Biochem Biophys Res Commun ; 712-713: 149955, 2024 Jun 18.
Article em En | MEDLINE | ID: mdl-38640737
ABSTRACT
We previously demonstrated a positive relation of secretory phospholipase A2 group IIA (sPLA2-IIA) with circulating high-density lipoprotein cholesterol (HDL-C) in patients with coronary artery disease, and sPLA2-IIA increased cholesterol efflux in THP-1 cells through peroxisome proliferator-activated receptor-γ (PPAR-γ)/liver X receptor α/ATP-binding cassette transporter A1 (ABCA1) signaling pathway. The aim of the present study was to examine the role of sPLA2-IIA over-expression on lipid profile in a transgenic mouse model. Fifteen apoE-/- and C57BL/7 female mice received bone marrow transplantation from transgenic SPLA2-IIA mice, and treated with specific PPAR-γ inhibitor GW9662. High fat diet was given after one week of bone marrow transplantation, and animals were sacrificed after twelve weeks. Immunohistochemical staining showed over-expression of sPLA2-IIA protein in the lung and spleen. The circulating level of HDL-C, but not that of low-density lipoprotein cholesterol (LDL-C), total cholesterol, or total triglyceride, was increased by sPLA2-IIA over-expression, and was subsequently reversed by GW9662 treatment. Over-expression of sPLA2-IIA resulted in augmented expression of cholesterol transporter ABCA1 at mRNA level in the aortas, and at protein level in macrophages, co-localized with macrophage specific antigen CD68. GW9662 exerted potent inhibitory effects on sPLA2-IIA-induced ABCA1 expression. Conclusively, we demonstrated the effects of sPLA2-IIA on circulating HDL-C level and the expression of ABCA1, possibly through regulation of PPAR-γ signaling in transgenic mouse model, that is in concert with the conditions in patients with coronary artery disease.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Camundongos Transgênicos / Transportador 1 de Cassete de Ligação de ATP / Molécula CD68 / Camundongos Endogâmicos C57BL Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Camundongos Transgênicos / Transportador 1 de Cassete de Ligação de ATP / Molécula CD68 / Camundongos Endogâmicos C57BL Idioma: En Ano de publicação: 2024 Tipo de documento: Article