ArticleExperimental and therapeutic medicine2022
Exogenous spermine inhibits high glucose/oxidized LDL-induced oxidative stress and macrophage pyroptosis by activating the Nrf2 pathway.
Article in Experimental and therapeutic medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Dietary Spermidine Mitigates Radiation-Induced Intestinal Injury by Reshaping the Microbiota-Barrier-Inflammation Axis.Food science & nutrition · 2026Article
- Cellular and Molecular Mechanisms of Hyperglycemia-Induced Atherosclerosis and Intervention Strategies of Chinese Herbal Medicine.Drug design, development and therapy · 2026Review
- Myhre Syndrome Presenting With Congenital Proximal Radioulnar Synostosis: A Case Report.Cureus · 2026Article
- Article
- Single-Cell Analysis Reveals a Critical Role for Macrophage Epsins in Regulating the Origin of Foam Cells in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Cyclodextrin attenuates atherosclerosis by diminishing gasdermin D (GSDMD)-mediated pyroptosis.Scientific reports · 2025Article
- Sex- and age-dependent neurovascular abnormalities linked to neuroinflammation lead to exacerbated post-ischemic brain injury in Marfan syndrome mice.Redox biology · 2025Article
- Macrophage pyroptosis in atherosclerosis: therapeutic potential.Acta biochimica et biophysica Sinica · 2025Review
- Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals.BMC biology · 2024Article
- The dance of macrophage death: the interplay between the inevitable and the microenvironment.Frontiers in immunology · 2024Review
- Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.Kidney diseases (Basel, Switzerland) · 2023Review
- Kynurenic acid inhibits macrophage pyroptosis by suppressing ROS production via activation of the NRF2 pathway.Molecular medicine reports · 2023Article
- New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.International journal of molecular sciences · 2023Review
- Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines.Life (Basel, Switzerland) · 2023Article
- The emerging role of pyroptosis-related inflammasome pathway in atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2022Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence suggests that macrophage pyroptosis promotes the progression of diabetic atherosclerosis. Spermine, a natural cellular metabolite, demonstrates a protective effect against cardiovascular diseases. However, whether spermine has a protective effect against macrophage pyroptosis caused by high glucose (HG) and oxidized low-density lipoprotein (ox-LDL) conditions remains to be elucidated. To investigate the protective effect of spermine and the related underlying mechanism, THP-1 macrophages were treated with HG/ox-LDL, spermine, or the specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385. Cell viability was detected using CCK-8, cell membrane permeability was analyzed using lactate dehydrogenase (LDH) and Hoechst/propidium iodide staining and pyroptosis-related gene and protein expression levels were evaluated using polymerase chain reaction and western blot analysis. Spermine showed a potent preventive effect on THP-1 macrophage pyroptosis and oxidative stress induced by HG/ox-LDL. Cells treated with spermine showed increased cell viability, reduced reactive oxygen species (ROS) production, decreased LDH levels in the supernatant and reduced cell swelling. In addition, spermine significantly reduced NLR family pyrin domain containing 3, cleaved caspase-1, N-gasdermin D and IL-1β expression, as well as IL-1β levels in the supernatant. This demonstrated that the inhibition of pyroptosis and oxidative stress due to spermine was Nrf2 dependent. Furthermore, spermine enhanced Nrf2 nuclear translocation, thereby increasing heme oxygenase-1 and NADPH quinone oxidoreductase-1 expression, which subsequently reduced ROS production. In addition, the anti-pyroptotic and antioxidant effects of spermine were reversed by ML385 inhibition of Nrf2. It was concluded that spermine prevented macrophage pyroptosis and increased ROS overproduction by activating the Nrf2 pathway. The data suggested that spermine may be a potential novel drug for the treatment of diabetic atherosclerosis because it targets macrophage pyroptosis.
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