ArticleFrontiers in neurology2020
20-HETE Enzymes and Receptors in the Neurovascular Unit: Implications in Cerebrovascular Disease.
Article in Frontiers in neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- G protein-coupled receptor 75 mediates depression-like behaviors and HPA axis hyperactivity through an excitatory arcuate-paraventricular nucleus circuit.Acta pharmacologica Sinica · 2026Article
- Calcium dysregulation in neurovascular function in Alzheimer's disease: mechanisms, therapeutic targets.GeroScience · 2026Review
- Maternal obesity induces macrophage to myofibroblast transition in kidneys of male offspring through a pathway driven by 20-hydroxyeicosatetraenoic acid.Nature communications · 2026Article
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Sex-dependent role of 20-HETE synthesis in outcome from ischemic stroke in rats.Physiological reports · 2026Article
- Anatomical and Neuronal Distribution of the G-Coupled Protein Receptor 75 mRNA in the Mouse Central Nervous System.The European journal of neuroscience · 2026Article
- The polyunsaturated fatty acid and oxylipin plasma signature of aneurysmal subarachnoid haemorrhage, case-control study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Differential Gene and Protein Expressions Responsible for Vasomotor Signaling Provide Mechanistic Bases for the Opposite Flow-Induced Responses of Pre- and Post-Circle of Willis Arteries.Life (Basel, Switzerland) · 2025Article
- GPR75: Advances, Challenges in Deorphanization, and Potential as a Novel Drug Target for Disease Treatment.International journal of molecular sciences · 2025Review
- The role of astrocytes in ischemic stroke - mechanisms, functions and treatment.Frontiers in cell and developmental biology · 2025Review
- "No-reflow" phenomenon in acute ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Gpr75 knockout mice display age-dependent cone photoreceptor cell loss.Journal of neurochemistry · 2023Article
- Mice deficient for G-protein-coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall.Journal of neurochemistry · 2023Article
- Longitudinal characterization of cerebral hemodynamics in the TgF344-AD rat model of Alzheimer's disease.GeroScience · 2023Article
- Hyperoxia evokes pericyte-mediated capillary constriction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Article
- The blood-brain barrier and the neurovascular unit in subarachnoid hemorrhage: molecular events and potential treatments.Fluids and barriers of the CNS · 2022Review
- Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, reverses cerebrovascular dysfunction and cognitive impairments in 18-mo-old diabetic animals.American journal of physiology. Heart and circulatory physiology · 2022Article
- The adducin saga: pleiotropic genomic targets for precision medicine in human hypertension-vascular, renal, and cognitive diseases.Physiological genomics · 2022Review
- Uncovering the signalling, structure and function of the 20-HETE-GPR75 pairing: Identifying the chemokine CCL5 as a negative regulator of GPR75.British journal of pharmacology · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
20-HETE is a potent vasoconstrictor that is implicated in the regulation of blood pressure, cerebral blood flow and neuronal death following ischemia. Numerous human genetic studies have shown that inactivating variants in the cytochrome P450 enzymes that produce 20-HETE are associated with hypertension, stroke and cerebrovascular disease. However, little is known about the expression and cellular distribution of the cytochrome P450A enzymes (CYP4A) that produce 20-HETE or the newly discovered 20-HETE receptor (GPR75) in the brain. The present study examined the cell types and regions in the rat forebrain that express CYP4A and GPR75. Brain tissue slices from Sprague Dawley (SD), Dahl Salt-Sensitive (SS) and CYP4A1 transgenic rat strains, as well as cultured human cerebral pericytes and cerebral vascular smooth muscle cells, were analyzed by fluorescent immunostaining. Tissue homogenates from these strains and cultured cells were examined by Western blot. In the cerebral vasculature, CYP4A and GPR75 were expressed in endothelial cells, vascular smooth muscle cells and the glial limiting membrane of pial arteries and penetrating arterioles but not in the endothelium of capillaries. CYP4A, but not GPR75, was expressed in astrocytes. CYP4A and GPR75 were both expressed in a subpopulation of pericytes on capillaries. The diameters of capillaries were significantly decreased at the sites of first and second-order pericytes that expressed CYP4A. Capillary diameters were unaffected at the sites of other pericytes that did not express CYP4A. These findings implicate 20-HETE as a paracrine mediator in various components of the neurovascular unit and are consistent with 20-HETE's emerging role in the regulation of cerebral blood flow, blood-brain barrier integrity, the pathogenesis of stroke and the vascular contributions to cognitive impairment and dementia. Moreover, this study highlights GPR75 as a potential therapeutic target for the treatment of these devastating conditions.
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