ArticleJournal of cellular and molecular medicine2015
Foam cell-derived 4-hydroxynonenal induces endothelial cell senescence in a TXNIP-dependent manner.
Article in Journal of cellular and molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Investigation of oxidized low-density lipoprotein (oxLDL)-induced inflammation in atherosclerosis using a paper-based immune-vascular model.Analytical and bioanalytical chemistry · 2026Article
- Stacked human aortic endothelial cells induce atherosclerotic fatty streaks and release proinflammatory cytokines and chemokines.Mechanobiology in medicine · 2026Article
- TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effect ofInternational journal of endocrinology · 2026Article
- Acetylation reader BRD4-driven TXNIP transcription enhances NLRP3 inflammasome activation in PCOS.Cellular and molecular life sciences : CMLS · 2025Article
- PPARs in atherosclerosis: The spatial and temporal features from mechanism to druggable targets.Journal of advanced research · 2025Review
- Effect of Cordyceps militaris extract containing cordycepin on the adipogenesis and lipolysis of adipocytes.FEBS open bio · 2025Article
- Lipid peroxidation products induce carbonyl stress, mitochondrial dysfunction, and cellular senescence in human and murine cells.Aging cell · 2025Article
- Impact of Inducible Nitric Oxide Synthase Activation on Endothelial Behavior under Magnesium Deficiency.Nutrients · 2024Article
- Reactive Carbonyl Species and Protein Lipoxidation in Atherogenesis.Antioxidants (Basel, Switzerland) · 2024Review
- The Peroxidation of Lipids, Cellular Senescence and Aging.Journal of aging science · 2024Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- VDUP1 Deficiency Promotes the Severity of DSS-Induced Colitis in Mice by Inducing Macrophage Infiltration.International journal of molecular sciences · 2023Article
- The Role of Txnip in Mediating Low-Magnesium-Driven Endothelial Dysfunction.International journal of molecular sciences · 2023Article
- Extracellular Vesicles and Cardiac Aging.Advances in experimental medicine and biology · 2023Article
- Review
- Adipose Tissue Plasticity in Response to Pathophysiological Cues: A Connecting Link between Obesity and Its Associated Comorbidities.International journal of molecular sciences · 2022Review
- Article
- TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook.Oxidative medicine and cellular longevity · 2022Review
- Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19.Antioxidants (Basel, Switzerland) · 2021Article
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular endothelial cell (VEC) senescence is considered an early event in the development of atherosclerotic lesions. Stressful stimuli, in particular oxidative stress, have been linked to premature senescence in the vasculature. Foam cells are a major source of reactive oxygen species and may play a role in the induction of VEC senescence; hence, we investigated their involvement in the induction of VEC senescence in a co-culture transwell system. Primary bovine aortic endothelial cells, exposed to the secretome of THP-1 monocyte-derived foam cells, were analysed for the induction of senescence. Senescence associated β-galactosidase activity and the expression of p16 and p21 were increased, whereas phosphorylated retinoblastoma protein was reduced. This senescent phenotype was mediated by 4-hydroxnonenal (4-HNE), a lipid peroxidation product secreted from foam cells; scavenging of 4-HNE in the co-culture medium blunted this effect. Furthermore, both foam cells and 4-HNE increased the expression of the pro-oxidant thioredoxin-interacting protein (TXNIP). Molecular manipulation of TXNIP expression confirmed its involvement in foam cell-induced senescence. Previous studies showed that peroxisome proliferator-activated receptor (PPAR)δ was activated by 4-hydroalkenals, such as 4-HNE. Pharmacological interventions supported the involvement of the 4-HNE-PPARδ axis in the induction of TXNIP and VEC senescence. The association of TXNIP with VEC senescence was further supported by immunofluorescent staining of human carotid plaques in which the expression of both TXNIP and p21 was augmented in endothelial cells. Collectively, these findings suggest that foam cell-released 4-HNE activates PPARδ in VEC, leading to increased TXNIP expression and consequently to senescence.
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