Abstract 178: Cilostazol Attenuated Inflammation and Matrix Metalloproteases Induced by TNF-α
Objective: Previously, we demonstrated that cilostazol, a phosphodiesterase-3 inhibitor, attenuated AngII-induced abdominal aortic aneurysms (AAAs) in male apolipoprotein E (apoE) deficient mice. However, the mechanism of this protective effect is unknown. The purpose of this study was to elucidate the effect of cilostazol on inflammation and MMPs in several cell types present in AAAs.
Methods and Results: First, aortic endothelial cells (ECs) were isolated from male apoE deficient mice. After confluence from 3 to 5 passages, ECs were incubated with saline, TNF-alpha, or TNF-alpha/cilostazol for 24 hours. Many inflammatory genes, such as MCP-1, IL-1beta, COX-2, ICAM-1 and VCAM-1, were increased by TNF-alpha, but the enhancements of them were attenuated by co-treatment of cilostazol. Western blot revealed that cilostazol attenuated TNF-alpha-induced ICAM-1 protein expression. Second, aortic vascular smooth muscle cells (VSMCs) were isolated from male apoE deficient mice. Cultured VSMCs were incubated with saline, TNF-alpha, or TNF-alpha/cilostazol for 24 hours. Similar to ECs, cilostazol decreased gene expression of inflammation such as MCP-1, COX-2, iNOS, OPN, and gene expression of MMP-2 and -9 that were induced by TNF-alpha. Third, we harvested peritoneal macrophages from male apoE deficient mice. 24 hours incubation with TNF-alpha induced MMP-2 and MMP-9 gene expression. Co-treatment with cilostazol attenuated gene expression of these proteases.
Conclusion: Our results indicate that cilostazol exerts anti-inflammatory effect on selected cell types that promote arterial vascular wall inflammation. This effect might, in part, contribute to attenuated AngII-induced AAAs in male apoE deficient mice.
Author Disclosures: R. Umebayashi: None. H.A. Uchida: None. H. Makino: None.
- © 2014 by American Heart Association, Inc.