PMID- 11455205
OWN - NLM
STAT- MEDLINE
DCOM- 20010809
LR  - 20180815
IS  - 1018-1172 (Print)
IS  - 1018-1172 (Linking)
VI  - 38
IP  - 4
DP  - 2001 Jul-Aug
TI  - Monocyte chemotactic protein 1 amplifies serotonin-induced vascular smooth muscle 
      cell proliferation.
PG  - 341-9
AB  - Monocyte chemotactic protein 1 (MCP-1), which is synthesized by vascular cells, 
      is a chemoattractant for monocytes and has been implicated in a wide range of 
      acute and chronic inflammatory processes characterized by monocyte infiltration, 
      including atherosclerosis. However, it is unclear whether MCP-1 is able to 
      modulate vascular smooth muscle cell (VSMC) proliferation. We assessed the effect 
      of MCP-1 on VSMC proliferation and its interaction with serotonin (5-HT), a 
      mitogen for VSMCs. Growth-arrested VSMCs were stimulated with different 
      concentrations of MCP-1 (25-200 ng/ml) and 5-HT (5 and 50 microM) in serum-free 
      medium. DNA synthesis in VSMCs was measured by [3H]thymidine incorporation. 5-HT 
      at concentrations of 5 and 50 microM significantly stimulated DNA synthesis by 
      1.8- and 2.1-fold over the control value, respectively (p < 0.0001). However, 
      MCP-1 at the concentrations tested did not have any significant effect on DNA 
      synthesis. Even though MCP-1 (50 ng/ml) by itself is not mitogenic, when added to 
      5-HT, it significantly amplified the mitogenic effect of 5-HT compared with that 
      of 5-HT alone (p < 0.0001). The 5-HT2A receptor antagonist sarpogrelate (10 
      microM) and its major metabolite M-1 (0.1 microM), pertussis toxin (10 ng/ml), 
      Src family protein tyrosine kinase (PTK) inhibitor PP2 (1 microM), protein kinase 
      C (PKC) inhibitor Ro31-8220 (0.1 microM) and mitogen-activated protein kinase 
      (MAPK) kinase inhibitor PD098059 (10 microM) significantly inhibited the 
      mitogenic effect of 5-HT and its interaction with MCP-1. Anti-MCP-1 antibody (2 
      microg/ml) and the Janus kinase 2 (JAK2) inhibitor AG490 (10 microM) 
      significantly inhibited the interaction of MCP-1 with 5-HT. Further, the 
      amplified mitogenic effect of 5-HT with MCP-1 was completely reversed by the 
      combined use of sarpogrelate with anti-MCP-1 antibody. Our results suggest that 
      MCP-1 amplifies the mitogenic effect of 5-HT on VSMCs. The mitogenic effect of 
      5-HT may be mediated by the G protein-Src family PTK-PKC-MAPK pathway. The 
      activation of the JAK2/signal transducer and activator of transcription 3 pathway 
      by MCP-1 in addition to the MAPK pathway by 5-HT may explain the potentiating 
      effect of MCP-1 on 5-HT-induced mitogenesis.
CI  - Copyright 2001 S. Karger AG, Basel
FAU - Watanabe, T
AU  - Watanabe T
AD  - Department of Internal Medicine, Division of Cardiology, University of 
      Texas-Houston Health Science Center, Houston, Tex 77030, USA.
FAU - Pakala, R
AU  - Pakala R
FAU - Katagiri, T
AU  - Katagiri T
FAU - Benedict, C R
AU  - Benedict CR
LA  - eng
PT  - Journal Article
PL  - Switzerland
TA  - J Vasc Res
JT  - Journal of vascular research
JID - 9206092
RN  - 0 (Antibodies)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Indoles)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Succinates)
RN  - 0 (Tyrphostins)
RN  - 0 (Virulence Factors, Bordetella)
RN  - 0 (alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide)
RN  - 19P708E787 (sarpogrelate)
RN  - 333DO1RDJY (Serotonin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.4.2.31 (Pertussis Toxin)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - W9A0B5E78O (Ro 31-8220)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Cell Count
MH  - Cell Division/*drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/immunology/*pharmacology
MH  - Culture Media, Serum-Free
MH  - DNA/biosynthesis
MH  - Drug Synergism
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - GTP-Binding Proteins/physiology
MH  - Humans
MH  - Indoles/pharmacology
MH  - Janus Kinase 2
MH  - Male
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Muscle, Smooth, Vascular/*cytology/drug effects/metabolism
MH  - Pertussis Toxin
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - *Proto-Oncogene Proteins
MH  - Rabbits
MH  - Receptor, Serotonin, 5-HT2A
MH  - Receptors, Serotonin/drug effects/physiology
MH  - Serotonin/*pharmacology
MH  - Signal Transduction
MH  - Succinates/pharmacology
MH  - Tyrphostins/pharmacology
MH  - Virulence Factors, Bordetella/pharmacology
MH  - src-Family Kinases/antagonists & inhibitors
EDAT- 2001/07/17 10:00
MHDA- 2001/08/10 10:01
CRDT- 2001/07/17 10:00
PHST- 2001/07/17 10:00 [pubmed]
PHST- 2001/08/10 10:01 [medline]
PHST- 2001/07/17 10:00 [entrez]
AID - 51065 [pii]
AID - 10.1159/000051065 [doi]
PST - ppublish
SO  - J Vasc Res. 2001 Jul-Aug;38(4):341-9. doi: 10.1159/000051065.