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Updated: Apr 22, 2026
Porcine Model of Infrarenal Abdominal Aortic Aneurysm
Published on: November 21, 2019
5-Lipoxygenase pathway in experimental abdominal aortic aneurysms
Castigliano M Bhamidipati1, Carl A Whatling1, Gaurav S Mehta1
1From the Division of Thoracic and Cardiovascular Surgery, Department of Surgery (C.M.B., A.K.M., V.A.H., G.A.), Department of Surgery (G.S.M.), Division of Vascular and Endovascular Surgery, Department of Surgery (G.S., G.R.U.), Department of Molecular Physiology and Biological Physics (M.S., G.K.O.), Department of Molecular Physiology and Biological Physics, Robert M. Berne Cardiovascular Research Center (G.R.U., G.K.O., G.A.), and Department of Biomedical Engineering (G.A.), University of Virginia School of Medicine, Charlottesville; and Cardiovascular Disease Section, Bioscience Department, AstraZeneca R&D, Mölndal, Sweden (C.A.W.).
Inhibiting the 5-lipoxygenase (5-LO) pathway reduces abdominal aortic aneurysm (AAA) formation and progression. This pathway is a potential therapeutic target for treating AAAs.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Inflammation Biology
Background:
- The role of leukotriene production via the 5-lipoxygenase (5-LO) pathway in abdominal aortic aneurysm (AAA) pathophysiology is debated.
- The precise mechanism by which 5-LO influences AAA development remains unclear.
Purpose of the Study:
- To investigate the impact of 5-lipoxygenase (5-LO) pathway inhibition on abdominal aortic aneurysm (AAA) formation and progression.
- To elucidate the mechanism by which 5-LO contributes to AAA pathophysiology.
Main Methods:
- Utilized 5-LO knockout (5-LO(-/-)) mice and pharmacological 5-LO inhibition in elastase perfusion and angiotensin II-treated low-density lipoprotein receptor-deficient (LDLr(-/-)) mouse models of AAA.
- Analyzed aortic tissue for elastin preservation, 5-LO and matrix metalloproteinase-9 (MMP9) expression, and inflammatory cell infiltration.
- Examined the effect of early and delayed 5-LO inhibition on AAA progression in wild-type mice.
- Corroborated findings with human AAA and control aorta samples.
Main Results:
- Aneurysm formation was significantly attenuated in 5-LO(-/-) mice and in wild-type mice receiving 5-LO(-/-) bone marrow.
- Pharmacological 5-LO inhibition reduced aneurysm development, preserved elastin, and decreased 5-LO and MMP9-producing cells in multiple AAA models.
- 5-LO inhibition reduced polymorphonuclear leukocyte infiltration into the aortic wall.
- Delayed inhibition of 5-LO arrested the progression of small AAAs.
- Expression patterns of elastin and 5-LO in human AAA samples mirrored findings in mouse models.
Conclusions:
- Targeting the 5-lipoxygenase (5-LO) pathway, through genetic or pharmacological means, effectively attenuates aneurysm formation and prevents medial layer fragmentation in AAA models.
- Interruption of the 5-LO pathway can halt the progression of established small AAAs.
- The 5-LO pathway represents a promising therapeutic target for the treatment of abdominal aortic aneurysms.
