PMID- 10195928
OWN - NLM
STAT- MEDLINE
DCOM- 19990517
LR  - 20190831
IS  - 1079-5642 (Print)
IS  - 1079-5642 (Linking)
VI  - 19
IP  - 4
DP  - 1999 Apr
TI  - Temporal gradient in shear but not steady shear stress induces PDGF-A and MCP-1 
      expression in endothelial cells: role of NO, NF kappa B, and egr-1.
PG  - 996-1003
AB  - Three well-defined laminar flow profiles were created to distinguish the 
      influence of a gradient in shear and steady shear on platelet-derived growth 
      factor A (PDGF-A) and monocyte chemoattractant protein-1 (MCP-1) expression in 
      human endothelial cells. The flow profiles (16 dyne/cm2 maximum shear stress) 
      were ramp flow (shear stress smoothly transited at flow onset), step flow (shear 
      stress abruptly applied at flow onset), and impulse flow (shear stress abruptly 
      applied for 3 s only). Ramp flow induced only minor expression of PDGF-A and did 
      not increase MCP-1 expression. Step flow increased PDGF-A and MCP-1 mRNA levels 
      3- and 2-fold at 1.5 hours, respectively, relative to ramp flow. In contrast, 
      impulse flow increased PDGF-A and MCP-1 expression 6- and 7-fold at 1.5 hours, 
      and these high levels were sustained for at least 4 hours. These results indicate 
      that a temporal gradient in shear (impulse flow and the onset of step flow) and 
      steady shear (ramp flow and the steady component of step flow) stimulates and 
      diminishes the expression of PDGF-A and MCP-1, respectively. NO synthase 
      inhibitor NG-amino-L-arginine (L-NAA) was found to markedly enhance MCP-1 and 
      PDGF-A expression induced by step flow, but decrease their expression induced by 
      impulse flow, in a dose-dependent manner. NO donor spermine-NONOate (SPR/NO) 
      dose-dependently reduced the MCP-1 and PDGF-A expression induced by impulse flow. 
      Moreover, impulse flow was found to stimulate sustained (4 hours) I kappa B-alpha 
      degradation and egr-1 mRNA induction. L-NAA prevented I kappa B-alpha 
      degradation, whereas SPR/NO increased I kappa B-alpha resynthesis 2 hours after 
      impulse flow. Both L-NAA and SPR/NO inhibited the impulse flow inducibility of 
      egr-1 4 hours after the flow stimulation. The results show that both NO induced 
      by steady shear and NO donor inhibit temporal gradient in shear-induced MCP-1 and 
      PDGF-A expression by downregulation of their respective transcription factors NF 
      kappa B and egr-1, whereas NO induced by impulse flow stimulates MCP-1 and PDGF-A 
      expression by upregulation of the transcription factors. The above findings 
      suggest distinct roles of temporal gradient in shear and steady shear in 
      atherogenesis in vivo.
FAU - Bao, X
AU  - Bao X
AD  - Department of Bioengineering, University of California, San Diego, La Jolla, CA 
      92093-0412, USA.
FAU - Lu, C
AU  - Lu C
FAU - Frangos, J A
AU  - Frangos JA
LA  - eng
GR  - R01 HL040696/HL/NHLBI NIH HHS/United States
GR  - HL-40696/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arterioscler Thromb Vasc Biol
JT  - Arteriosclerosis, thrombosis, and vascular biology
JID - 9505803
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EGR1 protein, human)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (platelet-derived growth factor A)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Early Growth Response Protein 1
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - *Immediate-Early Proteins
MH  - Infant, Newborn
MH  - NF-kappa B/*physiology
MH  - Nitric Oxide/*physiology
MH  - Platelet-Derived Growth Factor/*biosynthesis/genetics
MH  - RNA, Messenger/biosynthesis
MH  - Rheology
MH  - Time Factors
MH  - Transcription Factors/genetics/*physiology
MH  - Umbilical Veins
OTO - NASA
OT  - Non-programmatic
EDAT- 1999/04/09 00:00
MHDA- 1999/04/09 00:01
CRDT- 1999/04/09 00:00
PHST- 1999/04/09 00:00 [pubmed]
PHST- 1999/04/09 00:01 [medline]
PHST- 1999/04/09 00:00 [entrez]
AID - 10.1161/01.atv.19.4.996 [doi]
PST - ppublish
SO  - Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):996-1003. doi: 
      10.1161/01.atv.19.4.996.