ArticleProceedings of the National Academy of Sciences of the United States of America2017
Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.
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Who cites it
130 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Demethylase FTO attenuates atherosclerotic plaque via upregulating ABCA1 and ABCG1 expression by targeting ATG5.Molecular medicine reports · 2026Article
- A miniature endovascular soft robot for active blood flow regulation in occluded vessels.Nature biomedical engineering · 2026Article
- Residual cardiovascular risk in coronary artery disease: from pathophysiology to established and novel therapies.Nature reviews. Cardiology · 2026Review
- Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects.Bioengineering (Basel, Switzerland) · 2026Review
- Endothelial Cell Autophagy Suppresses Metastasis In Mouse Mammary and Pancreatic Neuroendocrine Tumor Models.bioRxiv : the preprint server for biology · 2026Article
- Review
- Pharmacological Foundation and Novel Insights of Resveratrol in Cardiovascular System: A Review.Current cardiology reviews · 2026Review
- ATG7 vs. ATG5: Distinct autophagy pathways shaping TGF-β signaling and endothelial function.PloS one · 2026Article
- Linking autophagy to endothelial cell immunogenicity in transplant-associated ischemia-reperfusion injury.Transplant immunology · 2025Article
- Association of chaperone-mediated autophagy with the mechanisms of vascular calcification in diabetic nephropathy.Renal failure · 2025Article
- Aging microvasculature: Effects on immune cell trafficking and inflammatory diseases.The Journal of experimental medicine · 2025Review
- A Novel Function of NaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Sex-Specific Antioxidant and Anti-Inflammatory Protective Effects of AMPK in Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Endothelial major vault protein alleviates vascular remodeling via promoting Parkin-mediated mitophagy.Nature communications · 2025Article
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- Insight into the Mechanistic role of Colchicine in Atherosclerosis.Current atherosclerosis reports · 2025Review
- Review
- Naringenin Attenuates Ox-LDL-induced Injury in HUVECs by Regulating Lipophagy Partly through the SOCE Pathway.Current pharmaceutical design · 2025Article
- Cancer therapy-related cardiovascular aging: mechanisms, monitoring, and intervention strategies.Frontiers in cardiovascular medicine · 2025Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has been known for some time that atherosclerotic lesions preferentially develop in areas exposed to low SS and are characterized by a proinflammatory, apoptotic, and senescent endothelial phenotype. Conversely, areas exposed to high SS are protected from plaque development, but the mechanisms have remained elusive. Autophagy is a protective mechanism that allows recycling of defective organelles and proteins to maintain cellular homeostasis. We aimed to understand the role of endothelial autophagy in the atheroprotective effect of high SS. Atheroprotective high SS stimulated endothelial autophagic flux in human and murine arteries. On the contrary, endothelial cells exposed to atheroprone low SS were characterized by inefficient autophagy as a result of mammalian target of rapamycin (mTOR) activation, AMPKα inhibition, and blockade of the autophagic flux. In hypercholesterolemic mice, deficiency in endothelial autophagy increased plaque burden only in the atheroresistant areas exposed to high SS; plaque size was unchanged in atheroprone areas, in which endothelial autophagy flux is already blocked. In cultured cells and in transgenic mice, deficiency in endothelial autophagy was characterized by defects in endothelial alignment with flow direction, a hallmark of endothelial cell health. This effect was associated with an increase in endothelial apoptosis and senescence in high-SS regions. Deficiency in endothelial autophagy also increased TNF-α-induced inflammation under high-SS conditions and decreased expression of the antiinflammatory factor KLF-2. Altogether, these results show that adequate endothelial autophagic flux under high SS limits atherosclerotic plaque formation by preventing endothelial apoptosis, senescence, and inflammation.
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