PMID- 11121811
OWN - NLM
STAT- MEDLINE
DCOM- 20020312
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 49
IP  - 1
DP  - 2001 Jan
TI  - Transient interaction of activated platelets with endothelial cells induces 
      expression of monocyte-chemoattractant protein-1 via a p38 mitogen-activated 
      protein kinase mediated pathway. Implications for atherogenesis.
PG  - 189-99
AB  - OBJECTIVE: Activated platelets induce alterations of chemotactic and adhesive 
      properties of endothelial cells, a critical initial step in atherogenesis. We 
      investigated the effect of transient interaction of activated platelets with 
      cultured human umbilical vein endothelial cells (HUVECs) on secretion of monocyte 
      chemoattractant protein-1 (MCP-1), a key molecule in monocyte chemotaxis and 
      transmigration. METHODS AND RESULTS: Transient interaction of 
      alpha-thrombin-activated platelets with endothelial cells for 10-120 min 
      substantially induced endothelial secretion of MCP-1, monocyte chemotaxis and 
      adhesion to HUVECs. Platelet-induced secretion of MCP-1 and monocyte-endothelium 
      adhesion was reduced by the MAP kinase p38-specific inhibitor SB203580, but not 
      by other kinase inhibitors including PD98059, wortmannin, or rapamycin. In 
      addition, activated platelets induced transcription of a luciferase reporter 
      construct containing a MCP-1 promotor, an effect that could be inhibited by 
      SB203580. Overexpression of dominant-negative mutants of MAP kinase p38, 
      CSBP2-(D168A) and CSBP2-(T180E,Y182E) reduced platelet-induced expression of 
      MCP-1. CONCLUSIONS: Activation of the p38 MAP kinase and consecutive endothelial 
      secretion of MCP-1 induced through transient interaction of activated platelets 
      might play an important role in atherogenesis.
FAU - Dickfeld, T
AU  - Dickfeld T
AD  - Medical Department, Duke University, Durham, NC, USA.
FAU - Lengyel, E
AU  - Lengyel E
FAU - May, A E
AU  - May AE
FAU - Massberg, S
AU  - Massberg S
FAU - Brand, K
AU  - Brand K
FAU - Page, S
AU  - Page S
FAU - Thielen, C
AU  - Thielen C
FAU - Langenbrink, K
AU  - Langenbrink K
FAU - Gawaz, M
AU  - Gawaz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Pyridines)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Arteriosclerosis/*etiology
MH  - Blood Platelets/*physiology
MH  - Cell Adhesion/physiology
MH  - Cell Culture Techniques
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis, Leukocyte/physiology
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/genetics/*physiology
MH  - Monocytes/physiology
MH  - Platelet Activation/physiology
MH  - Pyridines/pharmacology
MH  - Translocation, Genetic
MH  - Umbilical Veins/cytology
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2000/12/21 11:00
MHDA- 2002/03/13 10:01
CRDT- 2000/12/21 11:00
PHST- 2000/12/21 11:00 [pubmed]
PHST- 2002/03/13 10:01 [medline]
PHST- 2000/12/21 11:00 [entrez]
AID - S0008-6363(00)00220-0 [pii]
AID - 10.1016/s0008-6363(00)00220-0 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2001 Jan;49(1):189-99. doi: 10.1016/s0008-6363(00)00220-0.