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

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...

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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
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cited_by cdi_FETCH-LOGICAL-c730t-ae7f73d40536654c8eec12027ee561d20041981090e81b1c0bdf559eb23df6113
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Hermansson, Cecilia
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Bergström, Göran
Hultén, Lillemor Mattsson
description 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.
doi_str_mv 10.1371/journal.pone.0088546
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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. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Göteborgs universitet</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vijil, Carolina</au><au>Hermansson, Cecilia</au><au>Jeppsson, Anders</au><au>Bergström, Göran</au><au>Hultén, Lillemor Mattsson</au><au>Aikawa, Elena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Arachidonate 15-lipoxygenase enzyme products increase platelet aggregation and thrombin generation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-12</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e88546</spage><epage>e88546</epage><pages>e88546-e88546</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24533104</pmid><doi>10.1371/journal.pone.0088546</doi><tpages>e88546</tpages><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2014-02, Vol.9 (2), p.e88546-e88546
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1497405623
source Publicly Available Content Database; PubMed
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
title Arachidonate 15-lipoxygenase enzyme products increase platelet aggregation and thrombin generation
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