PMID- 15525793
OWN - NLM
STAT- MEDLINE
DCOM- 20050405
LR  - 20181201
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 312
IP  - 3
DP  - 2005 Mar
TI  - Cilostazol prevents remnant lipoprotein particle-induced monocyte adhesion to 
      endothelial cells by suppression of adhesion molecules and monocyte 
      chemoattractant protein-1 expression via lectin-like receptor for oxidized 
      low-density lipoprotein receptor activation.
PG  - 1241-8
AB  - This study shows cilostazol effect to prevent remnant lipoprotein particle 
      (RLP)-induced monocyte adhesion to human umbilical vein endothelial cells 
      (HUVECs). Upon incubation of HUVECs with RLP (50 microg/ml), adherent monocytes 
      significantly increased by 3.3-fold with increased cell surface expression of 
      vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, 
      E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Cilostazol ( 
      approximately 1-100 microM) concentration dependently repressed these variables 
      as did (E)3-[(4-t-butylphenyl)sulfonyl]-2-propenenitrile (BAY 11-7085) (10 
      microM), a specific nuclear factor-kappaB (NF-kappaB) inhibitor. Cilostazol 
      effects were significantly antagonized by iberiotoxin (1 microM), a maxi-K 
      channel blocker. RLP significantly increased expression of lectin-like receptor 
      for oxidized low-density lipoprotein (LDL) (LOX-1) receptor protein. Upon 
      transfection with antisense LOX-1 oligodeoxynucleotide (As-LOX-1), LOX-1 receptor 
      expression was reduced, whereas HUVECs with sense LOX-1 oligodeoxynucleotide did 
      express high LOX-1 receptor. RLP-stimulated superoxide and tumor necrosis 
      factor-alpha levels were significantly lowered with decreased expression of 
      VCAM-1 and MCP-1 by transfection with As-LOX-1 as did polyinosinic acid (10 
      microg/ml, a LOX-1 receptor inhibitor). RLP significantly degraded inhibitory 
      kappaBalpha in the cytoplasm and activated nuclear factor-kappaB (NF-kappaB) p65 
      in the nucleus of HUVECs with increased luciferase activity of NF-kappaB, all of 
      which were reversed by cilostazol (10 microM), BAY 11-7085, and polyinosinic 
      acid. Together, cilostazol suppresses RLP-stimulated increased monocyte adhesion 
      to HUVECs by suppression of LOX-1 receptor-coupled NF-kappaB-dependent nuclear 
      transcription via mediation of the maxi-K channel opening.
FAU - Park, So Youn
AU  - Park SY
AD  - Department of Pharmacology, College of Medicine, Pusan National University, 
      Ami-Dong 1-Ga, SeoGu, Busan 602-739, Korea. kwhong@pusan.ac.kr
FAU - Lee, Jeong Hyun
AU  - Lee JH
FAU - Kim, Yong Ki
AU  - Kim YK
FAU - Kim, Chi Dae
AU  - Kim CD
FAU - Rhim, Byung Yong
AU  - Rhim BY
FAU - Lee, Won Suk
AU  - Lee WS
FAU - Hong, Ki Whan
AU  - Hong KW
LA  - eng
PT  - Journal Article
DEP - 20041103
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Large-Conductance Calcium-Activated Potassium Channels)
RN  - 0 (Lipoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (OLR1 protein, human)
RN  - 0 (Potassium Channels, Calcium-Activated)
RN  - 0 (Receptors, LDL)
RN  - 0 (Receptors, Oxidized LDL)
RN  - 0 (Scavenger Receptors, Class E)
RN  - 0 (Tetrazoles)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (remnant-like particle cholesterol)
RN  - 11062-77-4 (Superoxides)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - N7Z035406B (Cilostazol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Cell Adhesion/drug effects
MH  - Cell Adhesion Molecules/*analysis
MH  - Cells, Cultured
MH  - Chemokine CCL2/*analysis
MH  - Cholesterol/pharmacology
MH  - Cilostazol
MH  - Endothelial Cells/*cytology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Large-Conductance Calcium-Activated Potassium Channels
MH  - Lipoproteins/*antagonists & inhibitors/pharmacology
MH  - Monocytes/*physiology
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Potassium Channels, Calcium-Activated/drug effects
MH  - Receptors, LDL/*metabolism
MH  - Receptors, Oxidized LDL
MH  - Scavenger Receptors, Class E
MH  - Superoxides/metabolism
MH  - Tetrazoles/*pharmacology
MH  - Triglycerides/*antagonists & inhibitors/pharmacology
MH  - Tumor Necrosis Factor-alpha/biosynthesis
EDAT- 2004/11/05 09:00
MHDA- 2005/04/06 09:00
CRDT- 2004/11/05 09:00
PHST- 2004/11/05 09:00 [pubmed]
PHST- 2005/04/06 09:00 [medline]
PHST- 2004/11/05 09:00 [entrez]
AID - jpet.104.077826 [pii]
AID - 10.1124/jpet.104.077826 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2005 Mar;312(3):1241-8. doi: 10.1124/jpet.104.077826. Epub 
      2004 Nov 3.