ArticleiScience2020
GPAT4-Generated Saturated LPAs Induce Lipotoxicity through Inhibition of Autophagy by Abnormal Formation of Omegasomes.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The Protective Effects of the Autophagic and Lysosomal Machinery in Vascular and Valvular Calcification: A Systematic Review.International journal of molecular sciences · 2020Pooled it
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.Research square · 2026Article
- TMEM174 Deficiency Reduces Longevity by Promoting Phosphate-Driven Vascular Calcification.bioRxiv : the preprint server for biology · 2026Article
- Concentrated Growth Factor Induces ER Stress and Apoptosis by Increasing Ceramide Generation in Selected Tumour Cell Lines.Journal of cellular and molecular medicine · 2025Article
- Lipid droplet dynamics in type 2 diabetes and its complications: pathophysiological insights and therapeutic options.Lipids in health and disease · 2025Review
- High Co-Expression ofBiomedicines · 2025Article
- Identification and validation of mitochondrial endoplasmic reticulum membrane-related genes in atherosclerosis.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Saturated phosphatidic acids induce mTORC1-driven integrated stress response contributing to glucolipotoxicity in hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Synthesis of Autotaxin-Inhibiting Lipid Nanoparticles to Regulate Autophagy and Inflammatory Responses in Activated Macrophages.Tissue engineering and regenerative medicine · 2025Article
- Tetrahydropalmatine promotes macrophage autophagy by inhibiting the AMPK/mTOR pathway to attenuate atherosclerosis.Histology and histopathology · 2025Article
- Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD.JCI insight · 2024Article
- Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment.Cell death discovery · 2024Review
- Dialogue between mitochondria and endoplasmic reticulum-potential therapeutic targets for age-related cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Sulforaphane induces lipophagy through the activation of AMPK-mTOR-ULK1 pathway signaling in adipocytes.The Journal of nutritional biochemistry · 2022Article
- Article
- Mitochondria-Associated Endoplasmic Reticulum Membranes: Inextricably Linked with Autophagy Process.Oxidative medicine and cellular longevity · 2022Review
- Molecular Dysfunctions of Mitochondria-Associated Endoplasmic Reticulum Contacts in Atherosclerosis.Oxidative medicine and cellular longevity · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Excessive levels of saturated fatty acids are toxic to vascular smooth muscle cells (VSMCs). We previously reported that mice lacking VSMC-stearoyl-CoA desaturase (SCD), a major enzyme catalyzing the detoxification of saturated fatty acids, develop severe vascular calcification from the massive accumulation of lipid metabolites containing saturated fatty acids. However, the mechanism by which SCD deficiency causes vascular calcification is not completely understood. Here, we demonstrate that saturated fatty acids significantly inhibit autophagic flux in VSMCs, contributing to vascular calcification and apoptosis. Mechanistically, saturated fatty acids are accumulated as saturated lysophosphatidic acids (LPAs) (i.e. 1-stearoyl-LPA) possibly synthesized through the reaction of GPAT4 at the contact site between omegasomes and the MAM. The accumulation of saturated LPAs at the contact site causes abnormal formation of omegasomes, resulting in accumulation of autophagosomal precursor isolation membranes, leading to inhibition of autophagic flux. Thus, saturated LPAs are major metabolites mediating autophagy inhibition and 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.