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

Autor: Yoshimi Hirose, Goro Miyakoda, Kiminobu Mitani, Tomohiro Yoshikawa, Keiko Okada, Hiromichi Takase, Reiko Okutsu, Youichi Yabuuchi, Masakazu Nagasawa
Rok vydání: 2009
Předmět:
CD36 Antigens
medicine.medical_specialty
Phosphodiesterase Inhibitors
CD36
Phosphodiesterase 3
Tetrazoles
Phosphodiesterase 3 Inhibitors
Mice
chemistry.chemical_compound
Internal medicine
Cyclic AMP
medicine
Animals
Scavenger receptor
Phosphodiesterase inhibitor
Protein Kinase Inhibitors
Cells
Cultured
Protein Kinase C
Foam cell
Dose-Response Relationship
Drug
biology
Scavenger Receptors
Class A
Cardiovascular Agents
Cyclic Nucleotide Phosphodiesterases
Type 3
Endocytosis
Cilostazol
Cyclic Nucleotide Phosphodiesterases
Type 4
Lipoproteins
LDL
Endocrinology
chemistry
Low-density lipoprotein
Macrophages
Peritoneal
biology.protein
lipids (amino acids
peptides
and proteins)
Cholesterol Esters
Phosphodiesterase 4 Inhibitors
Cardiology and Cardiovascular Medicine
Foam Cells
Lipoprotein
medicine.drug
Zdroj: Atherosclerosis. 204:405-411
ISSN: 0021-9150
DOI: 10.1016/j.atherosclerosis.2008.10.042
Popis: 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.
Databáze: OpenAIRE
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