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Lipoxygenases and Cardiovascular Diseases

  • Andrés Laguna-Fernández
  • Marcelo H. Petri
  • Silke Thul
  • Magnus BäckEmail author
Chapter
Part of the Progress in Inflammation Research book series (PIR)

Abstract

The lipoxygenase (LO) family of enzymes metabolize fatty acids into bioactive lipid mediators that exert potent actions on inflammatory reactions related to several cardiovascular diseases, such as atherosclerosis. The polyunsaturated omega-6 fatty acid arachidonic acid serves as a substrate for 5-LO, 12- and 15-LO, which catalyzes the formation of several bioactive lipid mediators. For example, 5-LO-derived leukotrienes transduce pro-inflammatory signaling in leukocytes and within the vascular wall. Targeting leukotriene receptors reduces experimental atherosclerosis, and pharmacoepidemiological studies indicate that leukotriene receptor antagonism is associated with a decreased cardiovascular risk. In contrast, sequential lipoxygenation of arachidonic acid yields lipoxins, which are anti-inflammatory and transduce the resolution of inflammation. The FPR2/ALX receptor is activated by both lipoxins and peptide agonists, and in murine models of atherosclerosis, FPR2/ALX deletion decreases atherosclerotic lesion size but increases atherosclerotic plaque instability. Finally, omega-3 essential fatty acids may serve as substrate for the LO enzymes yielding mediators that promote inflammation resolution, and omega-3 supplementation reduces experimental atherosclerosis. In conclusion, it is important to fully consider and explore all possible pathways of LO metabolism and their downstream metabolites when considering the role of the 5-, 12- and 15-LO pathways in cardiovascular disease.

Keywords

Atherosclerosis Inflammation Leukotriene Lipoxin Omega-3 Resolvin 

Notes

Acknowledgements

M.B. is supported by the Swedish Research Council (grant number 2014–2312); the Swedish Heart and Lung Foundation (grant numbers 20120474 and 20120827) and the Stockholm County Council (grant number 20140222). A.L.F. is a post-doctoral fellow within the CERIC Linnaeus Program. S.T. is supported by a post-doctoral fellowship from the Deutsche Forschungsgemeinschaft.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Andrés Laguna-Fernández
    • 1
    • 2
  • Marcelo H. Petri
    • 1
    • 2
  • Silke Thul
    • 1
    • 2
  • Magnus Bäck
    • 1
    • 2
    • 3
    Email author
  1. 1.Translational Cardiology, Center for Molecular Medicine, L8:03Karolinska University HospitalStockholmSweden
  2. 2.Department of MedicineKarolinska InstitutetStockholmSweden
  3. 3.Department of CardiologyKarolinska University HospitalStockholmSweden

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