ArticleAntioxidants & redox signaling2015
Disturbed Flow Induces Autophagy, but Impairs Autophagic Flux to Perturb Mitochondrial Homeostasis.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Mechanopriming by vascular stiffness and phenotypic reprogramming by disturbed flow: mechanobiology and clinical translation in atherosclerosis.Frontiers in cardiovascular medicine · 2026Pooled it
- Role of Flow-Sensitive Endothelial Genes in Atherosclerosis and Antiatherogenic Therapeutics Development.Journal of cardiovascular translational research · 2024Review
- Exercise mitigates flow recirculation and activates metabolic transducer SCD1 to catalyze vascular protective metabolites.Science advances · 2024Article
- Article
- Proteostasis and resilience in the mechanically-stressed vascular endothelium.Current opinion in physiology · 2023Review
- Modulation of the mitochondrial CaPhysiological reports · 2023Article
- Healthy versus Unhealthy Adipose Tissue Expansion: the Role of Exercise.Journal of obesity & metabolic syndrome · 2022Review
- Vascular Injury in the Zebrafish Tail Modulates Blood Flow and Peak Wall Shear Stress to Restore Embryonic Circular Network.Frontiers in cardiovascular medicine · 2022Article
- Vascular autophagy in health and disease.Basic research in cardiology · 2020Review
- A perfusion bioreactor-based 3D model of the subarachnoid space based on a meningeal tissue construct.Fluids and barriers of the CNS · 2019Article
- Elevated arterial shear rate increases indexes of endothelial cell autophagy and nitric oxide synthase activation in humans.American journal of physiology. Heart and circulatory physiology · 2019Article
- Advanced microscopy to elucidate cardiovascular injury and regeneration: 4D light-sheet imaging.Progress in biophysics and molecular biology · 2018Review
- Light-sheet Fluorescence Microscopy to Capture 4-Dimensional Images of the Effects of Modulating Shear Stress on the Developing Zebrafish Heart.Journal of visualized experiments : JoVE · 2018Article
- Role of GSK3β/α-synuclein axis in methamphetamine-induced neurotoxicity in PC12 cells.Toxicology research · 2018Article
- Flow-Responsive Vascular Endothelial Growth Factor Receptor-Protein Kinase C Isoform Epsilon Signaling Mediates Glycolytic Metabolites for Vascular Repair.Antioxidants & redox signaling · 2018Article
- Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion.World journal of gastroenterology · 2017Review
- Mitochondrial CaJournal of the Royal Society, Interface · 2017Review
- Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Shear Stress in Autophagy and Its Possible Mechanisms in the Process of Atherosclerosis.DNA and cell biology · 2017Review
- Blood Brothers: Hemodynamics and Cell-Matrix Interactions in Endothelial Function.Antioxidants & redox signaling · 2016Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
aimTemporal and spatial variations in shear stress are intimately linked with vascular metabolic effects. Autophagy is tightly regulated in intracellular bulk degradation/recycling system for maintaining cellular homeostasis. We postulated that disturbed flow modulates autophagy with an implication in mitochondrial superoxide (mtO2(•-)) production.
resultsIn the disturbed flow or oscillatory shear stress (OSS)-exposed aortic arch, we observed prominent staining of p62, a reverse marker of autophagic flux, whereas in the pulsatile shear stress (PSS)-exposed descending aorta, p62 was attenuated. OSS significantly increased (i) microtubule-associated protein light chain 3 (LC3) II to I ratios in human aortic endothelial cells, (ii) autophagosome formation as quantified by green fluorescent protein (GFP)-LC3 dots per cell, and (iii) p62 protein levels, whereas manganese superoxide dismutase (MnSOD) overexpression by recombinant adenovirus, N-acetyl cysteine treatment, or c-Jun N-terminal kinase (JNK) inhibition reduced OSS-mediated LC3-II/LC3-I ratios and mitochondrial DNA damage. Introducing bafilomycin to Earle's balanced salt solution or to OSS condition incrementally increased both LC3-II/LC3-I ratios and p62 levels, implicating impaired autophagic flux. In the OSS-exposed aortic arch, both anti-phospho-JNK and anti-8-hydroxy-2'-deoxyguanosine (8-OHdG) staining for DNA damage were prominent, whereas in the PSS-exposed descending aorta, the staining was nearly absent. Knockdown of ATG5 with siRNA increased OSS-mediated mtO2(•-), whereas starvation or rapamycin-induced autophagy reduced OSS-mediated mtO2(•-), mitochondrial respiration, and complex II activity. INNOVATION: Disturbed flow-mediated oxidative stress and JNK activation induce autophagy.
conclusionOSS impairs autophagic flux to interfere with mitochondrial homeostasis. Antioxid. Redox Signal. 23, 1207-1219.
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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.