5-lipoxygenase pathway in experimental abdominal aortic aneurysms

Castigliano 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

14 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

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Arachidonate 5-Lipoxygenase
Abdominal Aortic Aneurysm
Pancreatic Elastase
Aneurysm
Elastin
Perfusion
Pharmacology
Lipoxygenase Inhibitors
Leukotrienes
LDL Receptors
Matrix Metalloproteinase 9
Matrix Metalloproteinases
Angiotensin II
Aorta
Neutrophils
Bone Marrow

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Bhamidipati, C., Whatling, C. A., Mehta, G. S., Meher, A. K., Hajzus, V. A., Su, G., ... 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

5-lipoxygenase pathway in experimental abdominal aortic aneurysms. / Bhamidipati, Castigliano; Whatling, Carl A.; Mehta, Gaurav S.; Meher, Akshaya K.; Hajzus, Vanessa A.; Su, Gang; Salmon, Morgan; Upchurch, Gilbert R.; Owens, Gary K.; Ailawadi, Gorav.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 34, No. 12, 01.01.2014, p. 2669-2678.

Research output: Contribution to journalArticle

Bhamidipati, C, Whatling, CA, Mehta, GS, Meher, AK, Hajzus, VA, Su, G, Salmon, M, Upchurch, GR, Owens, GK & Ailawadi, G 2014, '5-lipoxygenase pathway in experimental abdominal aortic aneurysms', Arteriosclerosis, thrombosis, and vascular biology, vol. 34, no. 12, pp. 2669-2678. https://doi.org/10.1161/ATVBAHA.114.304016
Bhamidipati, Castigliano ; Whatling, Carl A. ; Mehta, Gaurav S. ; Meher, Akshaya K. ; Hajzus, Vanessa A. ; Su, Gang ; Salmon, Morgan ; Upchurch, Gilbert R. ; Owens, Gary K. ; Ailawadi, Gorav. / 5-lipoxygenase pathway in experimental abdominal aortic aneurysms. In: Arteriosclerosis, thrombosis, and vascular biology. 2014 ; Vol. 34, No. 12. pp. 2669-2678.
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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.",
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AU - Mehta, Gaurav S.

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AU - Hajzus, Vanessa A.

AU - Su, Gang

AU - Salmon, Morgan

AU - Upchurch, Gilbert R.

AU - Owens, Gary K.

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