5-lipoxygenase pathway in experimental abdominal aortic aneurysms

Castigliano M. Bhamidipati, Carl A. Whatling, Gaurav S. Mehta, Akshaya K. Meher, Vanessa A. Hajzus, Gang Su, Morgan Salmon, Gilbert R. Upchurch, Gary K. Owens, Gorav Ailawadi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective-The impact of leukotriene production by the 5-lipoxygenase (5-LO) pathway in the pathophysiology of abdominal aortic aneurysms (AAAs) has been debated. Moreover, a clear mechanism through which 5-LO influences AAA remains unclear.

Approach and Results-Aneurysm formation was attenuated in 5-LO-/- mice, and in lethally irradiated wild-type mice reconstituted with 5-LO-/- bone marrow in an elastase perfusion model. Pharmacological inhibition of 5-LO-attenuated aneurysm formation in both aortic elastase perfused wild-type and angiotensin II-treated LDLr-/- (low-density lipoprotein receptor) mice, with resultant preservation of elastin and fewer 5-LO and MMP9 (matrix metalloproteinase)-producing cells. Separately, analysis of wild-type mice 7 days after elastase perfusion showed that 5-LO inhibition was associated with reduced polymorphonuclear leukocyte infiltration to the aortic wall. Importantly, 5-LO inhibition initiated 3 days after elastase perfusion in wild-type mice arrested progression of small AAA. Human AAA and control aorta corroborated these elastin and 5-LO expression patterns.

Conclusions-Inhibition of 5-LO by pharmacological or genetic approaches attenuates aneurysm formation and prevents fragmentation of the medial layer in 2 unique AAA models. Administration of 5-LO inhibitor in small AAA slows progression of AAA. Targeted interruption of the 5-LO pathway is a potential treatment strategy in AAA.

Original languageEnglish (US)
Pages (from-to)2669-2678
Number of pages10
JournalArteriosclerosis, thrombosis, and vascular biology
Volume34
Issue number12
DOIs
StatePublished - Dec 11 2014

Keywords

  • Aneurysm
  • Aorta, abdominal
  • Arachidonate 5-lipoxygenase
  • Inflammation
  • Leukotriene B4 .

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of '5-lipoxygenase pathway in experimental abdominal aortic aneurysms'. Together they form a unique fingerprint.

  • Cite this

    Bhamidipati, C. M., Whatling, C. A., Mehta, G. S., Meher, A. K., Hajzus, V. A., Su, G., Salmon, M., Upchurch, G. R., Owens, G. K., & Ailawadi, G. (2014). 5-lipoxygenase pathway in experimental abdominal aortic aneurysms. Arteriosclerosis, thrombosis, and vascular biology, 34(12), 2669-2678. https://doi.org/10.1161/ATVBAHA.114.304016