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Diet-induced (epigenetic) changes in bone marrow augment atherosclerosis.

Erik van Kampen1, Armand Jaminon2, Theo J C van Berkel2

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High-fat diets induce lasting epigenetic changes in bone marrow (BM), increasing leukocyte counts and promoting atherosclerosis. These transplantable changes highlight the epigenome

Keywords:
CpG islandDNA methylationIRF8Pu.1hematopoiesismacrophage

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Area of Science:

  • Epigenetics
  • Hematology
  • Cardiovascular Science

Background:

  • Alterations in DNA methylation patterns in leukocytes are linked to atherosclerosis development and cardiovascular mortality.
  • Dietary factors can influence epigenetic modifications with potential long-term health consequences.

Purpose of the Study:

  • To investigate the long-term epigenetic changes in bone marrow (BM) cells induced by a high-fat Western-style diet (WTD).
  • To determine the consequences of these WTD-induced BM alterations on atherosclerosis susceptibility.

Main Methods:

  • Bone marrow (BM) from WTD-fed or control mice was transplanted into low-density lipoprotein receptor-deficient (LDLR KO) mice.
  • Epigenetic modifications (DNA methylation) in key hematopoietic genes were analyzed in recipient BM.
  • Hematopoietic cell populations, spleen size, and macrophage activation markers were assessed in peripheral blood and spleen.
  • Aortic root plaque size was measured to evaluate atherosclerosis development.

Main Results:

  • WTD BM transplantation led to hypomethylation of Pu.1 and IRF8 genes in recipient BM.
  • Recipients exhibited increased leukocyte counts, particularly monocytes and CD11c++ cells, and enlarged spleens with activated macrophages.
  • Mice receiving WTD BM showed a significant increase in aortic root plaque size without changes in serum cholesterol.
  • These findings demonstrate transplantable epigenetic alterations affecting the hematopoietic system and promoting atherosclerosis.

Conclusions:

  • Western-style diet (WTD) feeding induces persistent, transplantable epigenetic changes in bone marrow (BM).
  • These epigenetic modifications alter hematopoietic cell populations and increase susceptibility to atherosclerosis, independent of serum cholesterol levels.
  • Targeting the epigenome, alongside lipid reduction, may offer a novel therapeutic strategy for cardiovascular disorders.