ArticleBlood2011
12/15-Lipoxygenase gene knockout severely impairs ischemia-induced angiogenesis due to lack of Rac1 farnesylation.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 25 citations in OpenAlex.
- Protein farnesylation: from molecular mechanisms to therapeutic targeting in cancer, aging, and beyond.Frontiers in pharmacology · 2026Review
- Roles of Lipoxygenases in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- Serum metabolomics of hyperbilirubinemia and hyperuricemia in the Tibetan plateau has unique characteristics.Scientific reports · 2023Article
- Reply to Doboszewska et al.: The many faces of G-protein-coupled receptor 39.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- GPR39 deorphanization: The long and winding road to eicosanoids and a crosstalk between GPR39 and hedgehog signaling in angiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Angiogenesis after ischemic stroke.Acta pharmacologica Sinica · 2023Review
- Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.Communications biology · 2023Article
- IL-33 enhances Jagged1 mediated NOTCH1 intracellular domain (NICD) deubiquitination and pathological angiogenesis in proliferative retinopathy.Communications biology · 2022Article
- Emerging role of 12/15-Lipoxygenase (ALOX15) in human pathologies.Progress in lipid research · 2019Review
- Emerging cellular functions of the lipid metabolizing enzyme 15-Lipoxygenase-1.Cell proliferation · 2018Review
- Article
- Exploration of GGTase-I substrate requirements. Part 1: Synthesis and biochemical evaluation of novel aryl-modified geranylgeranyl diphosphate analogs.Bioorganic & medicinal chemistry letters · 2016Article
- The role of lipoxygenases in pathophysiology; new insights and future perspectives.Redox biology · 2015Review
- ROS-dependent Syk and Pyk2-mediated STAT1 activation is required for 15(S)-hydroxyeicosatetraenoic acid-induced CD36 expression and foam cell formation.Free radical biology & medicine · 2014Article
- YES, a Src family kinase, is a proximal glucose-specific activator of cell division cycle control protein 42 (Cdc42) in pancreatic islet β cells.The Journal of biological chemistry · 2014Article
- Rho GAPs and GEFs: controling switches in endothelial cell adhesion.Cell adhesion & migration · 2014Review
- 12-lipoxygenase activity plays an important role in PAR4 and GPVI-mediated platelet reactivity.Thrombosis and haemostasis · 2013Article
- Elevated level of pro-inflammatory eicosanoids and EPC dysfunction in diabetic patients with cardiac ischemia.Prostaglandins & other lipid mediators · 2013Article
- Phenotype-based high-content chemical library screening identifies statins as inhibitors of in vivo lymphangiogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
To understand the mechanisms by which 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) activates Rac1 in the induction of angiogenesis, we studied the role of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and αPix. 15(S)-HETE stimulated Rac1 in a sustained manner in human dermal microvascular endothelial cells (HDMVECs). Simvastatin, a potent inhibitor of HMG-CoA reductase, suppressed 15(S)-HETE-induced Rac1 activation in HDMVECs affecting their migration and tube formation. 15(S)-HETE by inducing HMG-CoA reductase expression caused increased farnesylation and membrane translocation of Rac1 where it became activated by Src-dependent αPix stimulation. Mevalonate rescued 15(S)-HETE-induced Rac1 farnesylation and membrane translocation in HDMVECs and the migration and tube formation of these cells from inhibition by simvastatin. Down-regulation of αPix inhibited 15(S)-HETE-induced HDMVEC migration and tube formation. Hind-limb ischemia induced Rac1 farnesylation and activation leading to increased angiogenesis and these effects were blocked by simvastatin and rescued by mevalonate in WT mice. In contrast, hind-limb ischemia failed to induce Rac1 farnesylation and activation as well as angiogenic response in 12/15-Lox(-/-) mice. Activation of Src and αPix were also compromised at least to some extent in 12/15-Lox(-/-) mice compared with WT mice in response to hind-limb ischemia. Together, these findings demonstrate for the first time that HMG-CoA reductase plays a determinant role in 12/15-Lox-induced angiogenesis.
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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.