ArticleJournal of lipid research2016
Oxidized LDL signals through Rho-GTPase to induce endothelial cell stiffening and promote capillary formation.
Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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
39 citing papers in PubMed, 52 citations in OpenAlex.
- The LDL pathway regulates actomyosin ring dynamics necessary for optimal cell wound repair.microPublication biology · 2026Article
- Lysophosphatidylcholine and lysophosphatidic acid as key messengers in atherosclerosis: from a lipid-inflammation vicious cycle to therapeutic translation.Frontiers in cardiovascular medicine · 2026Review
- Endothelial Stiffening Induced by CD36-Mediated Lipid Uptake Leads to Endothelial Barrier Disruption and Contributes to Atherosclerotic Lesions.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Complement factor H in molecular regulation of angiogenesis.Medical review (2021) · 2024Review
- The Placental Role in Gestational Diabetes Mellitus: A Molecular Perspective.TouchREVIEWS in endocrinology · 2024Review
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- Oxysterols as Biomarkers of Aging and Disease.Advances in experimental medicine and biology · 2024Article
- The role of miR-134-5p in 7-ketocholesterol-induced human aortic endothelial dysfunction.EXCLI journal · 2024Article
- lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis.Archives of medical science : AMS · 2024Article
- Vascular endothelial cellular mechanics under hyperglycemia and its role in tissue regeneration.Regenerative biomaterials · 2024Article
- Endothelial Function in Dyslipidemia: Roles of LDL-Cholesterol, HDL-Cholesterol and Triglycerides.Cells · 2023Review
- Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels.Open medicine (Warsaw, Poland) · 2023Article
- Caveolin-1 is a primary determinant of endothelial stiffening associated with dyslipidemia, disturbed flow, and ageing.Scientific reports · 2022Article
- The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System.International journal of molecular sciences · 2022Review
- Dietary 7-ketocholesterol exacerbates myocardial ischemia-reperfusion injury in mice through monocyte/macrophage-mediated inflammation.Scientific reports · 2022Article
- Chronic cholesterol depletion increases F-actin levels and induces cytoskeletal reorganization via a dual mechanism.Journal of lipid research · 2022Article
- Paradigms of endothelial stiffening in cardiovascular disease and vascular aging.Frontiers in physiology · 2022Review
- Review
- CD36 Signaling in Diabetic Cardiomyopathy.Aging and disease · 2021Review
- Lipoprotein-Induced Increases in Cholesterol and 7-Ketocholesterol Result in Opposite Molecular-Scale Biophysical Effects on Membrane Structure.Frontiers in cardiovascular medicine · 2021Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Endothelial biomechanics is emerging as a key factor in endothelial function. Here, we address the mechanisms of endothelial stiffening induced by oxidized LDL (oxLDL) and investigate the role of oxLDL in lumen formation. We show that oxLDL-induced endothelial stiffening is mediated by CD36-dependent activation of RhoA and its downstream target, Rho kinase (ROCK), via inhibition of myosin light-chain phosphatase (MLCP) and myosin light-chain (MLC)2 phosphorylation. The LC-MS/MS analysis identifies 7-ketocholesterol (7KC) as the major oxysterol in oxLDL. Similarly to oxLDL, 7KC induces RhoA activation, MLCP inhibition, and MLC2 phosphorylation resulting in endothelial stiffening. OxLDL also facilitates formation of endothelial branching networks in 3D collagen gels in vitro and induces increased formation of functional blood vessels in a Matrigel plug assay in vivo. Both effects are RhoA and ROCK dependent. An increase in lumen formation was also observed in response to pre-exposing the cells to 7KC, an oxysterol that induces endothelial stiffening, but not to 5α,6α epoxide that does not affect endothelial stiffness. Importantly, loading cells with cholesterol prevented oxLDL-induced RhoA activation and the downstream signaling cascade, and reversed oxLDL-induced lumen formation. In summary, we show that oxLDL-induced endothelial stiffening is mediated by the CD36/RhoA/ROCK/MLCP/MLC2 pathway and is associated with increased endothelial angiogenic activity.
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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.