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Published on: October 17, 2017

Lipa regulates myeloid differentiation and is essential for intra-plaque macrophage accumulation during atherogenesis

Tianhan Li1, Juanjuan Qiu2, Haoyue Zhang2

  • 1School of Basic Medical Medicine, Henan Medical University, Xinxiang, China; Laboratory of Genetic Regulators in the Immune System, School of Medical Technology, Henan Medical University, Xinxiang, China.

Journal of Lipid Research
|June 29, 2026
PubMed

Insights

Lysosomal acid lipase (LIPA) deficiency in macrophages significantly reduces atherosclerosis by decreasing foam cell formation and macrophage accumulation. This suggests LIPA is a potential therapeutic target for treating atherosclerosis.

Area of Science:

  • Cardiovascular Biology
  • Lipid Metabolism
  • Immunology

Background:

  • Lysosomal acid lipase (LIPA) is linked to coronary artery disease and highly expressed in macrophages, yet its role there is unclear.
  • Elevated LIPA in monocytes/macrophages and reduced levels in liver/plasma of at-risk individuals suggest a macrophage-specific role in atherosclerosis.
  • Investigating macrophage LIPA's influence on atherosclerosis is crucial, given challenges in studying LIPA-deficient models.

Purpose of the Study:

  • To determine the functional importance of macrophage Lysosomal acid lipase (LIPA) in the development of atherosclerosis.
  • To investigate the impact of LIPA deficiency and heterozygosity in macrophages on atherosclerosis progression in vivo.
  • To elucidate the molecular mechanisms underlying LIPA's role in macrophage lipid handling and foam cell formation.

Main Methods:

  • Generated LIPA-deficient (Lipa-/-) and heterozygous (Lipa+/-) mice on an Apoe-/- background to model atherosclerosis.
  • Utilized bone marrow transplantation to assess the role of macrophage-specific LIPA expression.
  • Employed flow cytometry, single-cell RNA sequencing, and in vitro macrophage assays to analyze lipid uptake, CD36 expression, and foam cell formation.

Main Results:

  • LIPA deficiency (Lipa-/-Apoe-/-) and heterozygosity (Lipa+/-Apoe-/-) significantly attenuated atherosclerosis, with protection mediated by bone marrow-derived cells.
  • Atheroprotection was associated with reduced foam cell formation and macrophage infiltration in plaques.
  • Macrophage-specific LIPA deficiency impaired lipid uptake and downregulated CD36 expression, without affecting hepatic lipid metabolism or differentiation.

Conclusions:

  • Macrophage Lysosomal acid lipase (LIPA) plays a critical role in promoting atherosclerosis by facilitating foam cell formation.
  • Targeting macrophage LIPA may offer a novel therapeutic strategy for atherosclerosis treatment.
  • LIPA deficiency impacts monocyte development and CD36 expression, key factors in macrophage lipid handling and plaque progression.

Keywords:
CD36LIPAatherosclerosisfoam cell formationmacrophages

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