title: The Arachidonate 15-Lipoxygenase Enzyme Product 15-HETE Is Present in Heart Tissue from Patients with Ischemic Heart Disease and Enhances Clot Formation.
abstract: Ischemic heart disease is a major cause of death and morbidity and the search for novel therapeutic targets is still required. We have previously shown that the enzyme arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), is highly expressed in ischemic heart tissue, but its role in the pathogenesis of ischemic heart disease is unclear. Here we showed that expression of ALOX15, but not ALOX12 or ALOX15B, was increased in ischemic versus non-ischemic human heart biopsy samples. A similar ALOX expression pattern was found in hypoxic human cardiomyocytes and cardiac endothelial cells. We also showed that levels of 15-HETE were significantly higher in ischemic versus non-ischemic human heart biopsy samples and showed a tendency to increase in serum from the patients with ischemic heart disease. Moreover, hypoxia increased the production of 15-HETE levels from human cardiomyocytes and cardiac endothelial cells. The hypoxia-induced increase in 15-HETE levels from human cardiomyocytes was inhibited by the ALOX15 inhibitor baicalein. Finally, by using intrinsic rotational thromboelastometry, we showed that human whole blood clotted faster in the presence of 15-HETE. In summary, we propose that increased ALOX15 expression in heart tissue under ischemic conditions may lead to increased production of 15-HETE, potentially contributing to thrombosis.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Lundqvist
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sandstedt
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Joakim
authors.initials: J
authors.lastname: Sandstedt
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Ruth
authors.initials: R
authors.lastname: Wickelgren
authors.affiliation: Translational Sciences, AstraZeneca R&D, Mölndal, Sweden.
authors.forename: Göran I
authors.initials: GI
authors.lastname: Hansson
authors.affiliation: Department of Cardiothoracic Surgery, Sahlgrenska University Hospital Gothenburg, Sweden and Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Jeppsson
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg and Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.|Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Lillemor Mattsson
authors.initials: LM
authors.lastname: Hultén
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D061251:Primary Cell Culture; D013916:Thrombelastography; D013927:Thrombosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001093:Arachidonate 15-Lipoxygenase