2. Academic Validation
  3. Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model

Modulation of lipid profile by secretory phospholipase A2 group IIA: Verification with a transgenic mouse model

  • Biochem Biophys Res Commun. 2024 Jun 18:712-713:149955. doi: 10.1016/j.bbrc.2024.149955.
Ling Liang 1,  Jing Song 2,  Shisheng Miao 3,  Qiang Xie 4,  Weihua Li 4,  Honglang Huang 5,  Dongyan Shen 6,  Wei Zhang 7
Affiliations

Affiliations

  • 1 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: [email protected].
  • 2 Laboratory Animal Center, Xiamen University, Xiamen, 361005, China.
  • 3 Department of Cardiology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361004, China.
  • 4 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 Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
  • 5 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.
  • 6 Cell Therapy Research Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China.
  • 7 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: [email protected].
PMID: 38640737 DOI: 10.1016/j.bbrc.2024.149955
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.

Keywords

ATP-Binding cassette transporter A1; Cholesterol efflux; High-density lipoprotein cholesterol; Peroxisome proliferator-activated receptor-γ; Secretory phospholipase A2 group IIA.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-16578
    99.87%, PPARγ Antagonist