PMID- 18821851
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20121115
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 418
IP  - 2
DP  - 2009 Mar 1
TI  - Apolipoprotein(a) stimulates vascular endothelial cell growth and migration and 
      signals through integrin alphaVbeta3.
PG  - 325-36
LID - 10.1042/BJ20080744 [doi]
AB  - Elevated plasma concentrations of Lp(a) [lipoprotein(a)] are an emerging risk 
      factor for atherothrombotic disease. Apo(a) [apolipoprotein(a)], the unique 
      glycoprotein component of Lp(a), contains tandem repeats of a plasminogen kringle 
      (K) IV-like domain. In the light of recent studies suggesting that apo(a)/Lp(a) 
      affects endothelial function, we evaluated the effects of apo(a)/Lp(a) on growth 
      and migration of cultured HUVECs (human umbilical-vein endothelial cells). Two 
      full-length r-apo(a) [recombinant apo(a)] variants (12K and 17K), as well as 
      Lp(a), were able to stimulate HUVEC growth and migration to a comparable extent; 
      17K r-apo(a) also decreased the levels of total and active transforming growth 
      factor-beta secreted by these cells. Using additional r-apo(a) variants 
      corresponding to deletions and/or site-directed mutants of various kringle 
      domains in the molecule, we were able to determine that the observed effects of 
      full-length r-apo(a) on HUVECs were dependent on the presence of a functional 
      lysine-binding site(s) in the apo(a) molecule. With respect to signalling events 
      elicited by apo(a) in HUVECs, we found that 17K treatment of the cells increased 
      the phosphorylation level of FAK (focal adhesion kinase) and MAPKs 
      (mitogen-activated protein kinases), including ERK 
      (extracellular-signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). 
      In addition, we showed that LM609, the function-blocking antibody to integrin 
      alphaVbeta3, abrogated the effects of 17K r-apo(a) and Lp(a) on HUVECs. Taken 
      together, the results of the present study suggest that the apo(a) component of 
      Lp(a) signals through integrin alphaVbeta3 to activate endothelial cells.
FAU - Liu, Lei
AU  - Liu L
AD  - Department of Biochemistry, Queen's University, Kingston, ON K7L3N6, Canada.
FAU - Craig, Andrew W
AU  - Craig AW
FAU - Meldrum, Heather D
AU  - Meldrum HD
FAU - Marcovina, Santica M
AU  - Marcovina SM
FAU - Elliott, Bruce E
AU  - Elliott BE
FAU - Koschinsky, Marlys L
AU  - Koschinsky ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Integrin alphaVbeta3)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.10.2 (Focal Adhesion Kinase 2)
RN  - EC 3.4.21.- (Apoprotein(a))
SB  - IM
MH  - Apoprotein(a)/*pharmacology
MH  - Cell Movement/*drug effects
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Endothelial Cells/*drug effects/metabolism/physiology
MH  - Focal Adhesion Kinase 2/metabolism
MH  - Humans
MH  - Integrin alphaVbeta3/*physiology
MH  - Lipoproteins, LDL/pharmacology
MH  - MAP Kinase Signaling System/drug effects
MH  - Phosphorylation
MH  - Recombinant Proteins/isolation & purification/pharmacology
MH  - Signal Transduction/drug effects
MH  - Transforming Growth Factor beta/metabolism
EDAT- 2008/09/30 09:00
MHDA- 2009/03/04 09:00
CRDT- 2008/09/30 09:00
PHST- 2008/09/30 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
PHST- 2008/09/30 09:00 [entrez]
AID - BJ20080744 [pii]
AID - 10.1042/BJ20080744 [doi]
PST - ppublish
SO  - Biochem J. 2009 Mar 1;418(2):325-36. doi: 10.1042/BJ20080744.