Suppression of experimental abdominal aortic aneurysm in a rat model by the phosphodiesterase 3 inhibitor cilostazol.

The present experiments sought to determine whether cilostazol, a selective inhibitor of cyclic adenosine monophosphate (cAMP) phosphodiesterase 3 (PDE3), suppressed elastase-induced abdominal aortic aneurysm (AAA) development in a rat model. Male Sprague-Dawley rats (n = 16/each group) were randomly distributed into three groups: sham-, saline-, and cilostazol-. Rats of saline and cilostazol groups underwent intra-aortic elastase perfusion to induce AAAs, while rats of sham-group were perfused with saline. Rats of cilostazol-group received cilostazol treatment (100 mgkg(-1)d(-1)) for the entire experimental period. The areas of the lumen of the aortas at the segment with maximum diameter were measured preperfusion and on d 7, 14 after perfusion. Systolic blood pressure was measured by tail-cuff technique. Aortic tissue samples were harvested on d 14 after intra-aortic perfusion and evaluated by reverse transcription-polymerase chain reaction and Western blot for matrix metalloproteinase-2, 9 (MMP-2, 9), by immunohistochemistry for nuclear factor kappa B (NF-κB), and by Gomori aldehyde fuchsin for elastin. Activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and level of reactive oxygen species (ROS) in these samples were also measured. On d 14, rats of saline-group had significantly increased aortic sizes compared with sham-group (P < 0.01), while, cilostazol treatment significantly reduced this increase (cilostazol- versus saline-, P < 0.01) without affecting blood pressure (P > 0.05). The expression of both MMP-2 and MMP-9 and the destruction of elastic fibers in aortic tissues were significantly decreased by cilostazol treatment (P < 0.05), probably through the suppression of NF-κB activation (P < 0.01). Consistently, cilostazol significantly inhibited NADPH oxidase activity (P < 0.01), accompanied by a reduced level of ROS (P < 0.01). Cilostazol retards experimental AAAs development independently of blood pressure reduction possibly by inhibiting proteolysis, inflammation, and oxidative stress. Selective PDE3 inhibition may offer an additional method to pharmacologically inhibit AAAs. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Qi Zhang, Jian-Hua Huang, Ren-Peng Xia, Xiao-Hui Duan, Yi-Bo Jiang, Qin Jiang, Wei-Jia Sun. Suppression of experimental abdominal aortic aneurysm in a rat model by the phosphodiesterase 3 inhibitor cilostazol. The Journal of surgical research. 2011 May 15;167(2):e385-93

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PMID: 21392796

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