ArticleAntioxidants (Basel, Switzerland)2021
CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells.
Article in Antioxidants (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Association of methylenetetrahydrofolate reductase C677T polymorphism with lacunar infarction: A systematic review and meta-analysis.Medicine · 2026Pooled it
- One-carbon metabolism and cardiovascular disease: Molecular mechanisms, genetic influences, and epigenetic regulation.Biochemistry and biophysics reports · 2026Review
- Folate in autism neurodevelopment.Frontiers in nutrition · 2026Review
- The association between serum uric acid and homocysteine is mediated by metabolic risk factors.Scientific reports · 2025Article
- Vitamins, Vascular Health and Disease.Nutrients · 2025Review
- Mapping the future: bibliometric insights into ferroptosis and diabetic nephropathy.Frontiers in physiology · 2025Review
- Cardiovascular aging: spotlight on mitochondria.American journal of physiology. Heart and circulatory physiology · 2024Review
- Oxidative Stress in Cardiovascular Disease and Comorbidities.Antioxidants (Basel, Switzerland) · 2022Article
- Multifunctions of CRIF1 in cancers and mitochondrial dysfunction.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Elevated plasma homocysteine levels can induce vascular endothelial dysfunction; however, the mechanisms regulating homocysteine metabolism in impaired endothelial cells are currently unclear. In this study, we deleted the essential mitoribosomal gene CR6 interacting factor 1 (CRIF1) in human umbilical vein endothelial cells (HUVECs) and mice to induce endothelial cell dysfunction; then, we monitored homocysteine accumulation. We found that CRIF1 downregulation caused significant increases in intracellular and plasma concentrations of homocysteine, which were associated with decreased levels of folate cycle intermediates such as 5-methyltetrahydrofolate (MTHF) and tetrahydrofolate (THF). Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Supplementation with folic acid did not restore DHFR expression levels or MTHF and homocysteine concentrations in endothelial cells with a CRIF1 deletion or DHFR knockdown. However, the overexpression of DHFR in CRIF1 knockdown endothelial cells resulted in decreased accumulation of homocysteine. Taken together, our findings suggest that CRIF1-deleted endothelial cells accumulated more homocysteine, compared with control cells; this was primarily mediated by the disruption of DHFR expression.
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Registered trials
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.