Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease
Zhao L, Grosser T, Fries S, Kadakia L, Wang H, Zhao J, Falotico R (2014)
Expert Review of Clinical Immunology 2(4): 649-658.
Zeitschriftenaufsatz
| Veröffentlicht | Englisch
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Autor*in
Zhao, Lei;
Grosser, TiloUniBi
;
Fries, Susanne;
Kadakia, Leena;
Wang, He;
Zhao, Jonathan;
Falotico, Robert
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Abstract / Bemerkung
The 12/15-lipoxygenase (LO) cascade governs the generation of 12-hydroperoxy-eicosatetraenoic acid (HPETE) and 15-HPETE from arachidonic acid. The 5-LO pathway plays a fundamental role in the biosynthesis of leukotrienes, essential inflammatory lipid mediators. Cyclooxygenase (COX)-1 and -2 biosynthetic pathways are responsible for prostaglandin and thromboxane formation. Experimental investigations in animal models using 12/15-LO deficient mice, 12/15-LO or 15-LO transgenic mice, or pharmacological 15-LO inhibition have all demonstrated the essential role of 12/15-LO in atherogenesis. The underlying mechanisms are linked to low-density lipoprotein oxidation, pro-inflammatory Th1 cytokine production and enhanced monocyte–endothelial cell interaction. Human genetic studies as well as disruption of the 5-LO gene in mouse models of hyperlipidemia revealed that 5-LO and 5-LO-activating protein are associated with risks of human cardiovascular disease, and that this cascade plays an important role in aortic aneurysm pathogenesis through leukotriene-mediated inflammatory chemokine production. COX-1 plays an active role in atherogenesis via thromboxane A2, while COX-2-derived prostaglandin (PGI2) protects against atherosclerosis in murine models. Recent data demonstrated that selective inhibition of COX-2 augments the risk of cardiovascular events in patients. Selective inhibition or blockade of selective components in these two enzymatic pathways through systemic drug delivery or medical device approaches (e.g., drug-eluting stents) may have therapeutic benefit against certain cardiovascular diseases.
Erscheinungsjahr
2014
Zeitschriftentitel
Expert Review of Clinical Immunology
Band
2
Ausgabe
4
Seite(n)
649-658
ISSN
1744-666X
eISSN
1744-8409
Page URI
https://pub.uni-bielefeld.de/record/2965345
Zitieren
Zhao L, Grosser T, Fries S, et al. Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease. Expert Review of Clinical Immunology. 2014;2(4):649-658.
Zhao, L., Grosser, T., Fries, S., Kadakia, L., Wang, H., Zhao, J., & Falotico, R. (2014). Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease. Expert Review of Clinical Immunology, 2(4), 649-658. https://doi.org/10.1586/1744666X.2.4.649
Zhao, Lei, Grosser, Tilo, Fries, Susanne, Kadakia, Leena, Wang, He, Zhao, Jonathan, and Falotico, Robert. 2014. “Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease”. Expert Review of Clinical Immunology 2 (4): 649-658.
Zhao, L., Grosser, T., Fries, S., Kadakia, L., Wang, H., Zhao, J., and Falotico, R. (2014). Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease. Expert Review of Clinical Immunology 2, 649-658.
Zhao, L., et al., 2014. Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease. Expert Review of Clinical Immunology, 2(4), p 649-658.
L. Zhao, et al., “Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease”, Expert Review of Clinical Immunology, vol. 2, 2014, pp. 649-658.
Zhao, L., Grosser, T., Fries, S., Kadakia, L., Wang, H., Zhao, J., Falotico, R.: Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease. Expert Review of Clinical Immunology. 2, 649-658 (2014).
Zhao, Lei, Grosser, Tilo, Fries, Susanne, Kadakia, Leena, Wang, He, Zhao, Jonathan, and Falotico, Robert. “Lipoxygenase and prostaglandin G/H synthase cascades in cardiovascular disease”. Expert Review of Clinical Immunology 2.4 (2014): 649-658.