title: Arachidonate 15-lipoxygenase enzyme products increase platelet aggregation and thrombin generation.
abstract: Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. We have previously shown that arachidonate 15-lipoxygenase B (ALOX15B) is highly expressed in atherosclerotic carotid plaques, and elucidation of mechanisms downstream of activated lipoxygenases may be relevant to our understanding of the genesis of atherosclerotic diseases. We examined 120 carotid plaques from patients with symptomatic carotid artery stenosis and showed that the extent of ALOX15B staining was significantly increased in carotid plaques with thrombosis. Impedance aggregometry analyses showed that the ALOX15B enzyme products 15-HETE and 15-HPETE increased platelet aggregation. By using a calibrated automatic thrombin assay, we showed that the ALOX15B products also increased both peak levels of thrombin and the total endogenous thrombin potential. Moreover, platelet aggregation was increased by addition of cell lysates from ischemic human macrophages, whereas platelet aggregation was reduced after knockdown of ALOX15B in human macrophages. Our data show that ALOX15B expression in human carotid plaques is associated with thrombus formation and that enzyme products of ALOX15B increase platelet aggregation and thrombin generation. We therefore propose that activated ALOX15B in macrophages may play a role in the induction of atherothrombotic events by increasing platelet aggregation and thrombin generation.
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vijil
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Hermansson
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Jeppsson
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Bergström
authors.affiliation: Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden ; 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; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D002138:Calibration; D002339:Carotid Arteries / Q000378:metabolism / Q000601:surgery; D016893:Carotid Stenosis / Q000378:metabolism*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000737:chemistry; D007150:Immunohistochemistry; D015289:Leukotrienes / Q000737:chemistry; D008054:Lipid Peroxides / Q000737:chemistry; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010974:Platelet Aggregation; D034741:RNA, Small Interfering / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D008054:Lipid Peroxides; D034741:RNA, Small Interfering; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase; D013917:Thrombin