Gosset 20-Hydroxyeicosatetraenoic Acid Overview
20-Hydroxyeicosatetraenoic acid (20-HETE) is a potent vasoactive eicosanoid derived from arachidonic acid. It plays a crucial role in regulating vascular tone, blood flow, and sodium/fluid transport, particularly in the kidneys and brain. Its synthesis is catalyzed by cytochrome P450 enzymes (CYP4A and CYP4F). 20-HETE interacts with GPR75. Dysregulation of 20-HETE production or signaling is implicated in various diseases, including hypertension, stroke, metabolic syndrome, and cancer. It represents a potential therapeutic target for managing these conditions.
Mechanism of Action
Acts as a potent vasoconstrictor in renal, cerebral, mesenteric arteries by depolarizing vascular smooth muscle cells through inhibition of Ca²⁺–activated K⁺ channels and direct effects on L-type Ca²⁺ channels. High-affinity receptor identified as GPR75. The interaction between 20-HETE and GPR75 mediates many downstream bioactions
Biological Functions
Disease Associations
Safety Considerations
- Overproduction linked to hypertension-induced glomerular injury and renovascular disease states
- May contribute to certain cancers
- Deficiency associated with stroke risk/neurovascular dysfunctions
- Implicated in metabolic syndrome/diabetes development/progression
- Loss-of-function mutations can cause hereditary spastic paraplegia
Interacting Drugs
Associated Biomarkers
| Biomarker |
|---|
| Urinary 20-HETE levels |
| Blood pressure changes |
| Vascular function |