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by claude@2026-07, 2026-07-14
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The study investigated how epigenetic regulators HDACs and TET demethylases influence early atherosclerotic plaque formation by promoting oxidized LDL-driven foam cell formation in macrophages. Using in vitro experiments with U937-derived macrophages treated with oxidized LDL, the authors found that TET1 directly supports foam cell formation, while HDAC2 plays a more indirect role; they used TET1 and HDAC2 inhibitors to map inter-regulated mechanisms controlling foam cell formation. In contrast, inhibition of TET2 under the same conditions did not reduce foam cell formation, and the work was limited to in vitro macrophage models. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
Atherosclerosis is a condition characterized by plaque growths in arteries, consisting of oxidized LDL (low-density lipoprotein) and localized cell cumulation. By the time of diagnosis for patients with atherosclerosis, the disease has often progressed into advanced stages. Statins are commonly prescribed; however, while these drugs can lower blood cholesterol levels, they cannot regress or stop the plaque growth. Currently, there are no treatments available to prevent the formation of new plaques. Such treatment options would require the identification of proteins that act during disease onset, initiating molecular mechanisms that promote plaque formation. Histone deacetylases (HDACs) and Ten Eleven Translocation (TET) demethylases are two important classes of epigenetic mediators. Some isoforms of these two classes of proteins have been found to transcriptionally regulate cellular inflammation, which may favor plaque formation. These transcriptional regulators seem to function early in the molecular mechanisms that are involved in disease progression. In the present work, we identified a clear role of these epigenetic proteins in foam cell formation. Foam cells have been implicated as part of the early steps which ultimately lead to atherosclerosis. Here we showed that in the presence of OxLDL (oxidized LDL), the protein isoform TET1 has a direct role in foam cell formation, while HDAC2 adopts a more indirect role. Using specific inhibitors of TET1 and HDAC2, we showed the inter-regulated molecular mechanisms between these proteins and how they regulate foam cell formation in vitro . In this study, we found that upon inhibition of TET1 in U937-derived macrophages, and subsequent foam cell formation via OxLDL treatment, a lower percentage of foam cells was observed. However, TET2 inhibition under the same treatment conditions had no effect on the inhibition of foam cell formation.
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Abstract
Atherosclerosis is a condition characterized by plaque growths in arteries, consisting of oxidized LDL (low-density lipoprotein) and localized cell cumulation. By the time of diagnosis for patients with atherosclerosis, the disease has often progressed into advanced stages. Statins are commonly prescribed; however, while these drugs can lower blood cholesterol levels, they cannot regress or stop the plaque growth. Currently, there are no treatments available to prevent the formation of new plaques. Such treatment options would require the identification of proteins that act during disease onset, initiating molecular mechanisms that promote plaque formation.
Histone deacetylases (HDACs) and Ten Eleven Translocation (TET) demethylases are two important classes of epigenetic mediators. Some isoforms of these two classes of proteins have been found to transcriptionally regulate cellular inflammation, which may favor plaque formation. These transcriptional regulators seem to function early in the molecular mechanisms that are involved in disease progression. In the present work, we identified a clear role of these epigenetic proteins in foam cell formation. Foam cells have been implicated as part of the early steps which ultimately lead to atherosclerosis. Here we showed that in the presence of OxLDL (oxidized LDL), the protein isoform TET1 has a direct role in foam cell formation, while HDAC2 adopts a more indirect role. Using specific inhibitors of TET1 and HDAC2, we showed the inter-regulated molecular mechanisms between these proteins and how they regulate foam cell formation in vitro.
In this study, we found that upon inhibition of TET1 in U937-derived macrophages, and subsequent foam cell formation via OxLDL treatment, a lower percentage of foam cells was observed. However, TET2 inhibition under the same treatment conditions had no effect on the inhibition of foam cell formation.
Competing Interest Statement
The authors have declared no competing interest.
8: Abbreviations
- TET1
- Ten Eleven Translocation 1
- TET2
- Ten Eleven Translocation 2
- HDAC2
- Histone Deacetylase 2
- HDAC10
- Histone Deacetylase 10
- OxLDL
- Oxidized Low Density Lipoproteins
- PMA
- Phorbol 13-Myristate 12-Acetate
- FBS
- Fetal Bovine Serum
- PBMCs
- Peripheral Blood Mononuclear Cells
- NBF
- Neutral Buffered Formalin
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