ArticleAtherosclerosis2016
Restoration of autophagy in endothelial cells from patients with diabetes mellitus improves nitric oxide signaling.
Article in Atherosclerosis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 107 citations in OpenAlex.
- Proteostasis Decline and Redox Imbalance in Age-Related Diseases: The Therapeutic Potential of NRF2.Biomolecules · 2025Review
- Leonurine alleviates doxorubicin-induced myocarditis in mice via MAPK/ERK pathway inhibition.American journal of translational research · 2025Article
- LPI-GPR55 promotes endothelial cell activation and inhibits autophagy through inducing LINC01235 expression.Annals of medicine · 2024Article
- Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Autophagy as a Guardian of Vascular Niche Homeostasis.International journal of molecular sciences · 2024Review
- Effect of Spermidine on Endothelial Function in Systemic Lupus Erythematosus Mice.International journal of molecular sciences · 2024Article
- Nrf2 Connects Cellular Autophagy and Vascular Senescence in Atherosclerosis: A Mini-Review.Journal of lipid and atherosclerosis · 2024Review
- Autophagy alterations in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease: the evidence from human studies.Internal and emergency medicine · 2024Review
- Review
- Research Progress on Histone Deacetylases Regulating Programmed Cell Death in Atherosclerosis.Journal of cardiovascular translational research · 2024Review
- Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism.Journal of cardiovascular translational research · 2024Review
- PKCδ regulates the vascular biology in diabetic atherosclerosis.Cell communication and signaling : CCS · 2023Review
- Autophagy-urea cycle pathway is essential for the statin-mediated nitric oxide bioavailability in endothelial cells.Journal of food and drug analysis · 2023Article
- Caveolin-1 and Atherosclerosis: Regulation of LDLs Fate in Endothelial Cells.International journal of molecular sciences · 2023Review
- Activating P2Y1 receptors improves function in arteries with repressed autophagy.Cardiovascular research · 2023Article
- Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy.Frontiers in endocrinology · 2023Review
- Type 2 diabetes mellitus induced autophagic response within pulmonary tissue in the rat model.BioImpacts : BI · 2023Article
- Association between Serum Spermidine and TyG Index: Results from a Cross-Sectional Study.Nutrients · 2022Article
- Article
- Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.Metabolites · 2022Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEndothelial dysfunction contributes to cardiovascular disease in diabetes mellitus. Autophagy is a multistep mechanism for the removal of damaged proteins and organelles from the cell. Under diabetic conditions, inadequate autophagy promotes cellular dysfunction and insulin resistance in non-vascular tissue. We hypothesized that impaired autophagy contributes to endothelial dysfunction in diabetes mellitus. METHODS AND
resultsWe measured autophagy markers and endothelial nitric oxide synthase (eNOS) activation in freshly isolated endothelial cells from diabetic subjects (n = 45) and non-diabetic controls (n = 41). p62 levels were higher in cells from diabetics (34.2 ± 3.6 vs. 20.0 ± 1.6, P = 0.001), indicating reduced autophagic flux. Bafilomycin inhibited insulin-induced activation of eNOS (64.7 ± 22% to -47.8 ± 8%, P = 0.04) in cells from controls, confirming that intact autophagy is necessary for eNOS signaling. In endothelial cells from diabetics, activation of autophagy with spermidine restored eNOS activation, suggesting that impaired autophagy contributes to endothelial dysfunction (P = 0.01). Indicators of autophagy initiation including the number of LC3-bound puncta and beclin 1 expression were similar in diabetics and controls, whereas an autophagy terminal phase indicator, the lysosomal protein Lamp2a, was higher in diabetics. In endothelial cells under diabetic conditions, the beneficial effect of spermidine on eNOS activation was blocked by autophagy inhibitors bafilomycin or 3-methyladenine. Blocking the terminal stage of autophagy with bafilomycin increased p62 (P = 0.01) in cells from diabetics to a lesser extent than in cells from controls (P = 0.04), suggesting ongoing, but inadequate autophagic clearance.
conclusionInadequate autophagy contributes to endothelial dysfunction in patients with diabetes and may be a target for therapy of diabetic vascular disease.
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