Angiopoietin-1 aggravates atherosclerosis by inhibiting cholesterol efflux and promoting inflammatory response

Xiang Ou1, Jia-Hui Gao2, Lin-Hao He3

  • 1Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Medical Research Experiment Center, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, China; Department of Endocrinology, The First Hospital of Changsha, Changsha, Hunan 410005, China.

Insights

Angiopoietin-1 (Ang-1) worsens atherosclerosis by inhibiting cholesterol efflux through the Tie2/TFE3/LXRα pathway, increasing inflammation and plaque formation in ApoE-/- mice.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Atherosclerosis Research

Background:

  • Angiopoietin-1 (Ang-1) is a secreted protein primarily regulating angiogenesis.
  • While Ang-1 promotes atherosclerosis, its specific impact on lipid metabolism and inflammation in this context is not well understood.

Purpose of the Study:

  • To investigate the effects of Angiopoietin-1 on lipid metabolism, inflammation, and atherosclerosis progression.
  • To elucidate the molecular mechanisms underlying Ang-1's influence on cholesterol efflux and plaque development.

Main Methods:

  • ApoE-/- mice were treated with Ang-1 via lentiviral vectors; THP-1 derived macrophages were also used.
  • Assessed atherosclerotic plaque size, cholesterol efflux, reverse cholesterol transport (RCT), and inflammatory cytokine levels.
  • Utilized Oil red O, HE staining, immunofluorescence, [3H]-cholesterol assays, Western blot, qPCR, and ELISA.

Main Results:

  • Ang-1 significantly augmented atherosclerotic plaque formation and inhibited cholesterol efflux.
  • Ang-1 downregulated LXRα, ABCA1, and ABCG1 expression via the Tie2/TFE3 pathway, reducing HDL-C and RCT.
  • Ang-1 promoted lipid accumulation, increased pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, MCP-1), and induced M1 macrophage markers.

Conclusions:

  • Angiopoietin-1 adversely affects cholesterol efflux by decreasing ABCA1 and ABCG1 expression through the Tie2/TFE3/LXRα pathway.
  • This mechanism promotes inflammation and accelerates atherosclerosis progression.
  • Ang-1 plays a detrimental role in cardiovascular health by exacerbating lipid dysregulation and inflammatory responses in atherosclerosis.
Abstract

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