ArticleThe Journal of clinical investigation2020
12(S)-HETE mediates diabetes-induced endothelial dysfunction by activating intracellular endothelial cell TRPV1.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 62 citations in OpenAlex.
- Identification of a human mitochondrial isoform of TRPV1: a thermostat regulating mitochondrial maximal temperature?Cellular and molecular life sciences : CMLS · 2026Article
- A novel role for TRPV1 in macrophage giant cell formation.bioRxiv : the preprint server for biology · 2026Article
- Aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole attenuates pressure overload cardiac hypertrophy by activating the CYP1A1/19(S)-hydroxyeicosatetraenoic acid (HETE) and suppressing midchain-HETEs/G protein coupled receptor 31 pathways.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Endothelial cell responses in sepsis are attenuated by targeting truncated procalcitonin.Nature communications · 2026Article
- TRPV1 mediates mitochondrial dysfunction in hyperthermia-induced ameloblast mineralization defects.Frontiers in cell and developmental biology · 2026Article
- The Role of TRPV1 in Type 1 Diabetes.Biology · 2025Review
- DPP4 inhibition curbs systemic inflammation.Critical care (London, England) · 2025Observational
- Acacetin reduces endoplasmic reticulum stress through the P-eNOS/PERK signaling pathway to attenuate MGO-induced vascular endothelial cell dysfunction.FEBS open bio · 2025Article
- CaBiomedicines · 2025Review
- Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.Frontiers in pharmacology · 2025Review
- Empagliflozin-Pretreated MSC-Derived Exosomes Enhance Angiogenesis and Wound Healing via PTEN/AKT/VEGF Pathway.International journal of nanomedicine · 2025Article
- Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Role of TRP Channels in Metabolism-Related Diseases.International journal of molecular sciences · 2024Review
- The potential mechanism of action of gut flora and bile acids through the TGR5/TRPV1 signaling pathway in diabetic peripheral neuropathic pain.Frontiers in endocrinology · 2024Review
- Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models.Channels (Austin, Tex.) · 2023Review
- Whey Improves In Vitro Endothelial Mitochondrial Function and Metabolic Redox Status in Diabetic State.Antioxidants (Basel, Switzerland) · 2023Article
- Deciphering Complex Interactions in Bioactive Lipid Signaling.Molecules (Basel, Switzerland) · 2023Article
- A human TRPV1 genetic variant within the channel gating domain regulates pain sensitivity in rodents.The Journal of clinical investigation · 2023Article
- Relationship of PIEZO1 and PIEZO2 vascular expression with diabetic neuropathy.Frontiers in physiology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Patients with diabetes develop endothelial dysfunction shortly after diabetes onset that progresses to vascular disease underlying the majority of diabetes-associated comorbidities. Increased lipid peroxidation, mitochondrial calcium overload, and mitochondrial dysfunction are characteristics of dysfunctional endothelial cells in diabetic patients. We here identified that targeting the lipid peroxidation product 12(S)-hydroxyeicosatetraenoic acid-induced [12(S)-HETE-induced] activation of the intracellularly located cation channel transient receptor potential vanilloid 1 (TRPV1) in endothelial cells is a means to causally control early-stage vascular disease in type I diabetic mice. Mice with an inducible, endothelium-specific 12/15-lipoxygenase (12/15Lo) knockout were protected similarly to TRPV1-knockout mice from type 1 diabetes-induced endothelial dysfunction and impaired vascular regeneration following arterial injury. Both 12(S)-HETE in concentrations found in diabetic patients and TRPV1 agonists triggered mitochondrial calcium influx and mitochondrial dysfunction in endothelial cells, and 12(S)-HETE effects were absent in endothelial cells from TRPV1-knockout mice. As a therapeutic consequence, we found that a peptide targeting 12(S)-HETE-induced TRPV1 interaction at the TRPV1 TRP box ameliorated diabetes-induced endothelial dysfunction and augmented vascular regeneration in diabetic mice. Our findings suggest that pharmacological targeting of increased endothelial lipid peroxidation can attenuate diabetes-induced comorbidities related to vascular disease.
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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.