15‐Lipoxygenase‐2 is expressed in macrophages in human carotid plaques and regulated by hypoxia‐inducible factor‐1α

Abstract

These results demonstrate that 15-LOX-2 is highly expressed in human plaques and is correlated with the presence of macrophages and HIF-1alpha. 15-LOX-2 enzyme activity can be modulated by HIF-1alpha. Thus, increased expression of 15-LOX-2 in macrophages in hypoxic atherosclerotic plaque may enhance inflammation and the recruitment of inflammatory cells.

The Arachidonate 15-Lipoxygenase Enzyme Product 15-HETE Is Present in Heart Tissue from Patients with Ischemic Heart Disease and Enhances Clot Formation

“…In addition to the increased ALOX15 levels observed in hypoxic human cardiomyocytes and cardiac endothelial cells in the present study and in human smooth muscle cells in an earlier study [4], we have previously shown that ALOX15B protein levels are increased in macrophages from carotid atherosclerotic plaques and that hypoxic macrophages express active ALOX15 leading to 15-HETE production [25]. Thus, our data combined suggest that the local environment within vessels or atherosclerotic plaques could contribute to locally increased 15-HETE and thus potentiate thrombus formation.…”

“…Here we showed that both cardiomyocytes and cardiac endothelial cells could potentially contribute to the increased 15-HETE levels observed in ischemic heart tissue. We have previously shown that hypoxia also increases ALOX15 in human smooth muscle cells [4], and thus this cell type could also contribute to the increased 15-HETE levels in the ischemic human heart tissue.…”

“…One such example is 15-lipoxygenase (ALOX15), which is present in the human myocardium [1, 2] and we have previously shown that its expression is increased in ischemic heart tissue [2]. Furthermore, the structurally related enzyme ALOX15B, which is increased in hypoxic human macrophages and symptomatic atherosclerotic carotid plaques [3, 4] is known to associate with a history of atherothrombotic events [5]. …”

The Structure of Human 15-Lipoxygenase-2 with a Substrate Mimic

“…Recent data implicate the 15-LOX-2 isoform in the pathogenesis of atherosclerosis because mRNA and protein levels of this LOX have been shown to be high in human carotid plaques (6). In addition, 15-LOX-2 is expressed in macrophages (7,34,35), and expression is regulated by hypoxia-inducible factor-1␣ (35). Moreover, knockdown of 15-LOX-2 expression in human primary macrophages and in mice (in this case, the target was 8-LOX, the murine homologue of 15-LOX-2) decreased lipid accumulation and inflammation, hallmarks of atherosclerosis (8).…”

Effect of shock waves on macrophages: A possible role in tissue regeneration and remodeling

“…The human genome includes six functional lipoxygenase genes (ALOX15, ALOX15B, ALOX12, ALOX12B, ALOXE3, ALOX5), which encode for six different LOX isoforms [26]. M1 macrophages express ALOX5, which plays a major role in the biosynthesis of pro-inflammatory leukotrienes, while ALOX15, ALOX15B, and ALOX12 are expressed in M2 macrophages associated to resolution of inflammation [27] and in carotid plaque macrophages [28].…”