Atherosclerosis. 2009 Jun;204(2):405-11. Epub 2008 Nov 17.

Cilostazol inhibits modified low-density lipoprotein uptake and foam cell formation in mouse peritoneal macrophages.

Okutsu R, Yoshikawa T, Nagasawa M, Hirose Y, Takase H, Mitani K, Okada K, Miyakoda G, Yabuuchi Y.

Source

Free Radical Project, Otsuka Pharmaceutical Co. Ltd., Tokushima, Japan. r_okutsu@research.otsuka.co.jp

Abstract

Internalization of modified low-density lipoprotein (LDL) via macrophage scavenger receptors (e.g. scavenger receptor A and CD36) is thought to play a crucial role in the development of atherosclerotic lesions. Cilostazol, an antiplatelet agent with selective phosphodiesterase 3 inhibitory action, has been reported to ameliorate atherosclerosis in mouse models. However, the effect of cilostazol on modified LDL uptake in macrophages is not known. Thus, we investigated the effect of cilostazol on LDL uptake in mouse peritoneal macrophages (MPM). Cilostazol significantly inhibited oxidized and acetylated LDL uptake in MPM, while cyclic AMP (cAMP)-elevating agents, db-cAMP and other phosphodiesterase 3 or 4 inhibitors, did not inhibit the uptake. Cilostazol did not change cytosolic cAMP levels in MPM, and a protein kinase A (PKA) inhibitor did not influence the inhibitory effects of cilostazol. Cilostazol decreased scavenger receptor A but not CD36 expression. Moreover, cilostazol significantly inhibited foam cell formation, which was represented by an increase in esterified cholesterol content. In conclusion, cilostazol significantly inhibits the uptake of modified LDL and foam cell formation in mouse peritoneal macrophages, and the inhibitory effect of cilostazol can be induced in a cAMP- and PKA-independent manner.

PMID:: 19108834; [PubMed - indexed for MEDLINE]

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