| The 5-lipoxygenase/leukotriene pathway in preclinical models of cardiovascular disease. | |
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MedLine Citation:
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PMID: 20093252 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Leukotrienes (LTs) derived from 5-lipoxygenase (5-LO) activity are most widely known for their actions during acute inflammation and asthma. 5-LO/LT pathway involvement in cardiovascular disease (CVD) pathogenesis has come to the forefront based on provocative human genetic/population and animal studies leading to the hypothesis that this pathway promotes atherosclerosis, abdominal aortic aneurysm, and myocardial infarction/reperfusion injury via increased leucocyte chemotaxis, vascular inflammation and enhanced permeability, and subsequent tissue/matrix degeneration. A series of pre-clinical studies have tested this hypothesis by means of genetic or pharmacological inhibition of either the LT biosynthesis axis (5-LO, 5-LO-activating protein, LTA(4) hydrolase, LTC(4) synthase) or the cognate LT receptors. Here, we summarize, compare, and analyse these animal studies and relate their findings to human disease pathogenesis. We draw a complex picture of 5-LO/LT participation in cardiovascular disorders, which is further complicated by marked differences between species. Moreover, we discuss how the cytokine footprint of the respective pathological conditions determines the expression level and hence, the contribution of components of the pathway to the overall disease state. Current knowledge implies a role for 5-LO and LTs during the early/acute phase of CVD, but our understanding of a putative 5-LO/LT involvement in more advanced stages of CVD is limited, thereby preventing simple extrapolation of findings from animal studies to humans. |
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Authors:
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Daniel Poeckel; Colin D Funk |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review Date: 2010-01-21 |
Journal Detail:
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Title: Cardiovascular research Volume: 86 ISSN: 1755-3245 ISO Abbreviation: Cardiovasc. Res. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-20 Completed Date: 2010-07-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: England |
Other Details:
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Languages: eng Pagination: 243-53 Citation Subset: IM |
Affiliation:
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Department of Physiology, Queen's University, 433 Botterell Hall, Kingston, ON, Canada K7L 3N6. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aortic Aneurysm, Abdominal / enzymology, immunology Arachidonate 5-Lipoxygenase / genetics, metabolism* Atherosclerosis / enzymology, immunology Cardiovascular Diseases / enzymology*, genetics, immunology, therapy Disease Models, Animal Humans Leukotrienes / metabolism* Myocardial Reperfusion Injury / enzymology, immunology Signal Transduction* / genetics |
| Grant Support | |
ID/Acronym/Agency:
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MOP-68930//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Leukotrienes; EC 1.13.11.34/Arachidonate 5-Lipoxygenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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