Targeting cysteinyl-leukotrienes in abdominal aortic aneurysm

Prostaglandins Other Lipid Mediat. 2018 Nov:139:24-28. doi: 10.1016/j.prostaglandins.2018.09.007. Epub 2018 Sep 21.

Abstract

Abdominal aortic aneurysm (AAA) is an asymptomatic dilatation of the vessel wall exceeding the normal vessel diameter by 50%, accompanied by intramural thrombus formation. Since the aneurysm can rupture, AAA is a life-threatening vascular disease, which may be amenable to surgical repair. At present, no pharmacological therapy for AAA is available. The 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism leads to biosynthesis of leukotrienes (LTs), potent lipid mediators with pro-inflammatory biological actions. Among the LTs, cysteinyl-leukotrienes (cys-LT) are well-recognized signaling molecules in human asthma and allergic rhinitis. However, the effects of these molecules in cardiovascular diseases have only recently been explored. Drugs antagonizing the CysLT1 receptor, termed lukasts and typified by montelukast, are established therapeutics for clinical management of asthma. Lukasts are safe, well-tolerated drugs that can be administered during long time periods. Here we describe recent data indicating that montelukast may be used for prevention and treatment of AAA, thus representing a promising pharmacological tool for a deadly vascular disease with significant socio-economic impact.

Keywords: Abdominal aortic aneurysm; Asthma; Cysteinyl-leukotrienes; Montelukast; Receptor antagonist.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetates / therapeutic use*
  • Aortic Aneurysm, Abdominal / drug therapy*
  • Aortic Aneurysm, Abdominal / pathology
  • Arachidonate 5-Lipoxygenase / metabolism
  • Arachidonic Acid / metabolism
  • Blood Vessels / drug effects
  • Blood Vessels / pathology
  • Cyclopropanes
  • Cysteine / antagonists & inhibitors
  • Cysteine / biosynthesis
  • Cysteine / genetics
  • Humans
  • Leukotriene Antagonists / therapeutic use
  • Leukotrienes / biosynthesis
  • Leukotrienes / genetics
  • Quinolines / therapeutic use*
  • Receptors, Leukotriene / drug effects
  • Receptors, Leukotriene / genetics*
  • Sulfides
  • Thrombosis / drug therapy*
  • Thrombosis / pathology

Substances

  • Acetates
  • Cyclopropanes
  • Leukotriene Antagonists
  • Leukotrienes
  • Quinolines
  • Receptors, Leukotriene
  • Sulfides
  • cysteinyl-leukotriene
  • Arachidonic Acid
  • Arachidonate 5-Lipoxygenase
  • Cysteine
  • leukotriene D4 receptor
  • montelukast