15HETE

15-hydroxyeicosatetraenoic acid (15‑HETE) is a fatty acid metabolite derived from arachidonic acid by oxygenases of the lipoxygenase family. The most common synthetic pathway involves 15‑lipoxygenase (15‑LOX) which adds a hydroperoxy group at the 15‑carbon position. Secondary oxidation of the hydroperoxy intermediate can yield other 15‑hydroxy derivatives such as 15‑S‑HETE or 15‑R‑HETE, which differ in stereochemistry. In some species, leukocyte expressed 5‑LOX can also generate 15‑HETE through trans‑cellular metabolism with platelet 12‑LOX or macrophage 15‑LOX.

15‑HETE functions as a signaling molecule in a variety of biological contexts. In the immune system it attracts granulocytes and monocytes, enhances endothelial cell proliferation, and modulates platelet aggregation. In vascular biology it can induce vasorelaxation or vasoconstriction depending on the receptor context and cell type. In the nervous system 15‑HETE has been implicated in neuroinflammatory processes. In cancer biology it is often up‑regulated in malignant tissues, where it influences tumor growth, angiogenesis, and metastasis. The exact cellular receptors for 15‑HETE remain incompletely defined; the G protein‑coupled receptor GPR31 has been suggested as a mediator of some of its actions, but other signaling pathways involve intracellular protein kinase C and MAP kinase cascades.

Analytical detection of 15‑HETE is typically performed by gas chromatography–mass spectrometry or liquid chromatography–tandem mass spectrometry after lipid extraction. Quantification in biological fluids is often in the low nanomolar to sub‑micromolar range under physiological conditions. Because of its role in inflammation and disease, inhibitors of 15‑LOX and approaches that scavenge 15‑HETE are being explored as therapeutic strategies for conditions such as asthma, atherosclerosis, and certain cancers.