ArticleInternational journal of molecular sciences2021
AICAR Protects Vascular Endothelial Cells from Oxidative Injury Induced by the Long-Term Palmitate Excess.
Article in International journal of molecular sciences, 2021. 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, 23 citations in OpenAlex.
- Tacrolimus Inhibits Hepatic Ferroptosis Through Modulating SIRT7-Dependent NRF2 Activation in Diabetes.Antioxidants (Basel, Switzerland) · 2026Article
- Targeting AMPK Networks for Male Reproductive Health: Mechanisms and Emerging Therapies.Cells · 2026Review
- Palmitic but Not Oleic Acid Induces Pro-Inflammatory Dysfunction of Human Endothelial Cells from Different Vascular Beds In Vitro.International journal of molecular sciences · 2025Article
- Metabolic and Immune Crosstalk in Cardiovascular Disease.Circulation research · 2025Review
- Progress and perspectives of metabolic biomarkers in blood sample for diabetic microvascular complications.Metabolomics : Official journal of the Metabolomic Society · 2025Review
- Molecular Mechanism of Aerobic Exercise Ameliorating Myocardial Mitochondrial Injury in Mice with Heart Failure.International journal of molecular sciences · 2025Article
- ANT-Mediated Inhibition of the Permeability Transition Pore Alleviates Palmitate-Induced Mitochondrial Dysfunction and Lipotoxicity.Biomolecules · 2024Article
- Free Fatty Acids and Free Fatty Acid Receptors: Role in Regulating Arterial Function.International journal of molecular sciences · 2024Review
- Quantification of AICAR and study of metabolic markers after administration.RSC advances · 2024Article
- Shear Stress and the AMP-Activated Protein Kinase Independently Protect the Vascular Endothelium from Palmitate Lipotoxicity.Biomedicines · 2024Article
- The role of oxidative stress in diabetes mellitus-induced vascular endothelial dysfunction.Cardiovascular diabetology · 2023Review
- Canagliflozin Delays Aging of HUVECs Induced by Palmitic Acid via the ROS/p38/JNK Pathway.Antioxidants (Basel, Switzerland) · 2023Article
- In Vitro Modeling of Diabetes Impact on Vascular Endothelium: Are Essentials Engaged to Tune Metabolism?Biomedicines · 2022Review
- The Functionality of Apigenin as a Novel Cardioprotective Nutraceutical with Emphasize on Regulating Cardiac Micro RNAs:.Galen medical journal · 2022Article
- Methotrexate and cardiovascular prevention: an appraisal of the current evidence.Therapeutic advances in cardiovascular diseaseReview
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Hyperlipidemia manifested by high blood levels of free fatty acids (FFA) and lipoprotein triglycerides is critical for the progression of type 2 diabetes (T2D) and its cardiovascular complications via vascular endothelial dysfunction. However, attempts to assess high FFA effects in endothelial culture often result in early cell apoptosis that poorly recapitulates a much slower pace of vascular deterioration in vivo and does not provide for the longer-term studies of endothelial lipotoxicity in vitro. Here, we report that palmitate (PA), a typical FFA, does not impair, by itself, endothelial barrier and insulin signaling in human umbilical vein endothelial cells (HUVEC), but increases NO release, reactive oxygen species (ROS) generation, and protein labeling by malondialdehyde (MDA) hallmarking oxidative stress and increased lipid peroxidation. This PA-induced stress eventually resulted in the loss of cell viability coincident with loss of insulin signaling. Supplementation with 5-aminoimidazole-4-carboxamide-riboside (AICAR) increased endothelial AMP-activated protein kinase (AMPK) activity, supported insulin signaling, and prevented the PA-induced increases in NO, ROS, and MDA, thus allowing to maintain HUVEC viability and barrier, and providing the means to study the long-term effects of high FFA levels in endothelial cultures. An upgraded cell-based model reproduces FFA-induced insulin resistance by demonstrating decreased NO production by vascular endothelium.
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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.