Hetes

Hydroxyeicosatetraenoic acids (HETEs) are a family of oxidized derivatives of arachidonic acid, a 20-carbon polyunsaturated fatty acid. They are eicosanoids that act as signaling mediators in inflammation, immunity, and vascular biology. HETEs are produced when arachidonic acid is released from membrane phospholipids and oxygenated by enzymes such as lipoxygenases (LOX) or cytochrome P450 enzymes; non-enzymatic oxidation can also generate HETEs. The most studied isomers are 5-HETE, 12-HETE, and 15-HETE, formed by 5-LOX, 12-LOX, and 15-LOX, respectively. 5-HETE is a chemoattractant for neutrophils and a precursor to leukotrienes. 12-HETE and 15-HETE participate in platelet function, vascular reactivity, and modulation of inflammatory responses. 15-HETE can influence peroxisome proliferator-activated receptor signaling in some contexts.

In addition to LOX-derived HETEs, cytochrome P450 ω-hydroxylases generate other HETEs, such as 20-HETE, which has a role in regulating vascular tone and renal function. HETEs can affect endothelial permeability, smooth muscle contraction, angiogenesis, and immune cell behavior, with effects that are context-dependent and may be pro- or anti-inflammatory.

Clinical relevance of HETEs includes altered levels in inflammatory diseases, asthma, cardiovascular disease, and cancer. They are studied as potential biomarkers and as targets for therapeutic intervention, including LOX inhibitors and strategies that modulate arachidonic acid metabolism. See also eicosanoids, leukotrienes, LOX enzymes, and PPAR signaling.