ArticleThe Journal of clinical investigation2015
Saturated phosphatidic acids mediate saturated fatty acid-induced vascular calcification and lipotoxicity.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.Research square · 2026Article
- ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.bioRxiv : the preprint server for biology · 2026Article
- Intestinal stearoyl-CoA desaturase-2 is highly expressed and nutritionally regulated but dispensable for energy balance.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Article
- Study on biomarkers of homocysteine-induced transformation of vascular smooth muscle cells into foam cells.Scientific reports · 2026Article
- Exploring the Effects of Incorporating Different Bioactive Phospholipids into Messenger Ribonucleic Acid Lipid Nanoparticle (mRNA LNP) Formulations.ACS bio & med chem Au · 2025Article
- N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis.Cell communication and signaling : CCS · 2025Article
- Heart Failure Management in the Modern Era: A Comprehensive Review on Medical and Device-based Interventions.Current cardiology reviews · 2025Review
- A stearate-rich diet and oleate restriction directly inhibit tumor growth via the unfolded protein response.Experimental & molecular medicine · 2024Article
- Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD.JCI insight · 2024Article
- Lipid droplets and cellular lipid flux.Nature cell biology · 2024Review
- Mechanism of Obesity-Related Lipotoxicity and Clinical Perspective.Advances in experimental medicine and biology · 2024Review
- Article
- Glycerolipid Synthesis and Lipid Droplet Formation in the Endoplasmic Reticulum.Cold Spring Harbor perspectives in biology · 2023Review
- Role of Stearoyl-CoA Desaturase 1 in Cardiovascular Physiology.International journal of molecular sciences · 2023Review
- Selective involvement of UGGT variant: UGGT2 in protecting mouse embryonic fibroblasts from saturated lipid-induced ER stress.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- PI(18:1/18:1) is a SCD1-derived lipokine that limits stress signaling.Nature communications · 2022Article
- All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal.Life science alliance · 2022Article
- Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD.Molecular metabolism · 2021Review
- Serum free fatty acids are associated with severe coronary artery calcification, especially in diabetes: a retrospective study.BMC cardiovascular disorders · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Recent evidence indicates that saturated fatty acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unsaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully saturated phosphatidic acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.
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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.