ArticleMolecular medicine (Cambridge, Mass.)2023
Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder.
Article in Molecular medicine (Cambridge, Mass.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 61 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- Defining metabolic heterogeneity in polyendocrine metabolic ovarian syndrome based on the MTHFR C677T polymorphism: the potential pathway role of homocysteine.Journal of ovarian research · 2026Article
- Association between plasma homocysteine levels and P-wave dispersion in pediatric patients with hyperhomocysteinemia.European journal of pediatrics · 2026Article
- Amino Acid Metabolism in Health and Disease.MedComm · 2026Review
- Endoplasmic Reticulum Stress-Induced Endothelial Cell Pyroptosis Contributes to Pulmonary Vascular Remodeling and Pulmonary Arterial Hypertension via IRE1α/Caspase-3/GSDME Pathway.Journal of the American Heart Association · 2026Article
- [CHOP promotes hepatocyte pyroptosis by downregulating endoplasmic reticulophagy and enhancing endoplasmic reticulum-mitochondria interaction].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- PAX5 alleviates atherosclerosis by transcriptionally regulating GSDMD and inhibiting STAT3-mediated pyroptosis.Biology direct · 2026Article
- The prognostic value of hyperhomocysteinemia in IgA nephropathy.International urology and nephrology · 2026Article
- Homocysteine-induced endothelial dysfunction through mediating endoplasmic reticulum stress.The Journal of international medical research · 2026Article
- Sympathetic Overactivation Drives Neurogenic Alveolar Epithelial Pyroptosis via the PIEZO2-ER Stress Pathway in Acute Lung Injury Following Intracerebral Hemorrhage.CNS neuroscience & therapeutics · 2026Article
- Effects of Vitamin B6 and Folic Acid on Cardiometabolic Biomarkers and Cardiac Oxidative Stress in Homocysteine-Loaded Rats.Biomedicines · 2026Article
- Targeting Ferroptosis and Pyroptosis in Cardiovascular Diseases: Mechanisms and Therapeutic Implication.Journal of cardiovascular translational research · 2026Review
- Does preoperative homocysteine level influence the kidney functions after coronary artery bypass grafting?BMC cardiovascular disorders · 2026Article
- BHMT Protects Against Diabetic Cataracts by Reducing Homocysteine and Counteracting Endoplasmic Reticulum Stress in Lens Epithelial Cells.Applied biochemistry and biotechnology · 2026Article
- Decoding the complex nexus: the mechanistic interplay of hyperhomocysteinemia in brain aging and neurological disorders.Biogerontology · 2026Review
- Targeting amino acid metabolic pathways: a novel therapeutic strategy for hyperuricemia-associated complications.Amino acids · 2026Review
- Lycium barbarum polysaccharide inhibits Hcy-induced vascular smooth muscle cells migration and invasion via upregulation of KLF4.Scientific reports · 2026Article
- The importance of mitochondria and mitochondrial calcium signaling in health and disease: an updated outlook on inflammation.Journal of translational medicine · 2026Review
- Study on biomarkers of homocysteine-induced transformation of vascular smooth muscle cells into foam cells.Scientific reports · 2026Article
- CDC25C downregulation suppresses HCC growth via mitochondrial stress-induced autophagy and apoptosis.Scientific reports · 2026Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundElevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear.
methodsA hyperhomocysteinemia atherosclerotic model with ApoE
resultsWe found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1β, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis.
conclusionHomocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.