Arachidonate 15-lipoxygenase enzyme products increase platelet aggregation and thrombin generation

• Published in: PloS one 2014-02, Vol.9 (2), p.e88546-e88546
• Main Authors: Vijil, Carolina, Hermansson, Cecilia, Jeppsson, Anders, Bergström, Göran, Hultén, Lillemor Mattsson
• Format: Article
• Language: English
• Subjects: Acids; ACTIVATION; Aged; Agglomeration; Annan klinisk medicin; Arachidonate 15-lipoxygenase; Arachidonate 15-Lipoxygenase - metabolism; Arteriosclerosis; ATHEROSCLEROSIS; ATHEROTHROMBOSIS; Automation; Biological products; Biology; Blood & organ donations; Blood clots; Blood platelets; Calibration; Cardiac and Cardiovascular Systems; Cardiovascular disease; Cardiovascular diseases; Carotid arteries; Carotid Arteries - metabolism; Carotid Arteries - surgery; Carotid artery; Carotid Stenosis - metabolism; Clinical medicine; DISEASE; Enzymes; EXPRESSION; Female; Gene expression; Gene Silencing; Health aspects; Heart diseases; Hospitals; HUMAN MACROPHAGES; Humans; Hydroxyeicosatetraenoic Acids - chemistry; Immunohistochemistry; INFLAMMATION; Ischemia; ISCHEMIC-STROKE; Kardiologi; Leukotrienes - chemistry; Lipid Peroxides - chemistry; Lipoxygenase; Lysates; Macrophages; Macrophages - cytology; Macrophages - metabolism; Male; MECHANISMS; Medicine; Middle Aged; Morbidity; Mortality; Other Clinical Medicine; Patients; Phenotype; PLAQUES; Platelet Aggregation; RNA, Small Interfering - metabolism; Stenosis; Stroke; Systematic review; Thrombin; Thrombin - metabolism; Thromboembolism; Thrombosis; Thrombosis - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088546

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.