Angiotensin II-induced abdominal aortic aneurysm occurs independently of the 5-lipoxygenase pathway in apolipoprotein E-deficient mice.

Abstract

Genetic association studies and pathological analysis of cardiovascular disease specimens implicate a role for the 5-lipoxygenase (5-LO)/leukotriene (LT) pathway in human cardiovascular disease. Previously, we had detected a role for this pathway in the incidence and severity of hyperlipidemic, cholate-containing, diet-induced aortic aneurysm in mice. The goal of the present study was to assess the importance of the 5-LO/LT pathway in angiotensin II (Ang II)-induced murine abdominal aortic aneurysm (AAA) formation. Mice with either genetic (5-LO(-/-)) or pharmacological (MK-0591) inhibition of the 5-LO pathway on an apolipoprotein E-deficient (apoE(-/-)) background were subjected to a normal chow diet with infusion of Ang II (500 ng/kg/min) for 28 days for assessment of AAA incidence and severity. Ang II-induced marked aortic wall remodeling with an incidence of 32, 29 and 40% AAA formation in 5-LO(-/-) apoE(-/-), 5-LO(+/+)apoE(-/-) and 5-LO(+/+)apoE(-/-) mice treated with FLAP inhibitor MK-0591, respectively, with no statistically significant differences in incidence or severity between groups. Abrogation of the 5-LO pathway in mice indicates a lack of role of leukotrienes in Ang II-induced AAA pathogenesis stressing the need for additional non-rodent AAA pre-clinical models to be tested.

• Authors: Richard Yang Cao, Michael A Adams, Andreas J Habenicht, Colin D Funk
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) Vol. 84 Issue 1-2 Pg. 34-42 (Aug 2007) ISSN: 1098-8823 [Print] United States
• PMID: 17643886 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Chemokine CCL4
• Indoles
• Macrophage Inflammatory Proteins
• Quinolines
• Angiotensin II
• MK 0591
• Arachidonate 5-Lipoxygenase

Topics

• Angiotensin II (metabolism)
• Animals
• Aortic Aneurysm, Abdominal (metabolism)
• Apolipoproteins E (genetics, physiology)
• Arachidonate 5-Lipoxygenase (metabolism)
• Blood Pressure
• Chemokine CCL4
• Indoles (pharmacokinetics, pharmacology)
• Inflammation
• Macrophage Inflammatory Proteins (metabolism)
• Macrophages (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Models, Genetic
• Quinolines (pharmacokinetics, pharmacology)
• Time Factors