The four 9-HODE isomers, particularly under conditions of oxidative stress, may form together in cells and tissues; they have overlapping but not identical biological activities and significances.

A similar set of 13-Hydroxyoctadecadienoic acid (13-HODE) metabolites (13(S)-HODE), 13(R)-HODE, 13(S)-EE-HODE), and 13(R)-EE-HODE) also occurs naturally and, again particularly under conditions of oxidative stress, may form concurrently with 9-HODEs; these 13-HODEs also have overlapping and complementary but not identical activities with the 9-HODEs.

[1][2][3] COX-2 exhibits a greater preference for linoleic acid than does Cox-1 and is therefore credited with producing most of these products in cells expressing both COX enzymes.

9-HODE esterified to the sn-2 position of phosphatidylserine is subject to be released as free 9-HODE by the action of cytosol (see phospholipase A2 section on cPLA2) and therefore may serve as a storage pool that is mobilized by cell stimulation.

[25][26][27] This activation appears responsible for the ability of 13-HODE (and 9-HODE) to induce the transcription of PPARγ-inducible genes in human monocytes as well as to stimulate the maturation of these cells to macrophages.

9(S)-HODE and with progressively lesser potencies 9(S)-HpODE, a racemic mixture of 9-HODE, 13(S)-HpODE, and 13(S)-HODE directly activate human (but not mouse) GPR132 (i.e. G protein coupled receptor 132 or G2A) in Chinese hamster ovary cells made to express these receptors; 9(S)-HODE was also a more potent stimulator of human G2A than a series of mono-hydroxy arachidonic acid metabolites.

That is, the free radical oxidation of linoleic acid makes these products which then proceed to contribute to the tissue injury, DNA damage, and/or systemic dysfunctions that characterize the diseases.

[42][43][44][45][46] Furthermore, certain of these HODE-related products may serve as signals to activate pathways that combat the reactive oxygen species and in this and other ways the oxidative stress.

9(S)-HODE, 9(R)-HODE, and 9-oxoODE, along with the other OXLAMs, appear to act through the TRPV1 receptor (see above section on Direct actions) mediate the perception of acute and chronic pain induced by heat, UV light, and inflammation in the skin of rodents.

9-HODEs, 13-HODEs, and low density lipoprotein which has been oxidized so that it contains HODEs stimulate the expression of interleukin 1β mRNA in and its extracellular release from human peripheral blood monocyte-derived macrophages; interleukin 1β is implicated in the proliferation of smooth muscle cells that occurs in atherosclerosis and contributes to blood vessel narrowing.