PMID- 30566391
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20211204
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 316
IP  - 3
DP  - 2019 Mar 1
TI  - Coagulation factor XI induces Ca(2+) response and accelerates cell migration in 
      vascular smooth muscle cells via proteinase-activated receptor 1.
PG  - C377-C392
LID - 10.1152/ajpcell.00426.2018 [doi]
AB  - Activated coagulation factor XI (FXIa) is a serine proteinase that plays a key 
      role in the intrinsic coagulation pathway. The analysis of FXI-knockout mice has 
      indicated the contribution of FXI to the pathogenesis of atherosclerosis. 
      However, the underlying mechanism remains unknown. We hypothesized that FXIa 
      exerts vascular smooth muscle effects via proteinase-activated receptor 1 
      (PAR(1)). Fura-2 fluorometry revealed that FXIa elicited intracellular Ca(2+) 
      signal in rat embryo aorta smooth muscle A7r5 cells. The influx of extracellular 
      Ca(2+) played a greater role in generating Ca(2+) signal than the Ca(2+) release 
      from intracellular stores. The FXIa-induced Ca(2+) signal was abolished by the 
      pretreatment with atopaxar, an antagonist of PAR(1), or 
      4-amidinophenylmethanesulfonyl fluoride (p-APMSF), an inhibitor of proteinase, 
      while it was also lost in embryonic fibroblasts derived from PAR(1)(-/-) mice. 
      FXIa cleaved the recombinant protein containing the extracellular region of 
      PAR(1) at the same site (R45/S46) as that of thrombin, a canonical PAR(1) 
      agonist. The FXIa-induced Ca(2+) influx was inhibited by diltiazem, an L-type 
      Ca(2+) channel blocker, and by siRNA targeted to Ca(V)1.2. The FXIa-induced 
      Ca(2+) influx was also inhibited by GF109203X and rottlerin, inhibitors of 
      protein kinase C. In a wound healing assay, FXIa increased the rate of cell 
      migration by 2.46-fold of control, which was partly inhibited by atopaxar or 
      diltiazem. In conclusion, FXIa mainly elicits the Ca(2+) signal via the 
      PAR(1)/Ca(V)1.2-mediated Ca(2+) influx and accelerates the migration in vascular 
      smooth muscle cells. The present study provides the first evidence that FXIa 
      exerts a direct cellular effect on vascular smooth muscle.
FAU - Liu, Wenhua
AU  - Liu W
AD  - Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University , 
      Kagawa , Japan.
FAU - Hashimoto, Takeshi
AU  - Hashimoto T
AD  - Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University , 
      Kagawa , Japan.
FAU - Yamashita, Tetsuo
AU  - Yamashita T
AD  - Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University , 
      Kagawa , Japan.
FAU - Hirano, Katsuya
AU  - Hirano K
AUID- ORCID: 0000-0003-0164-1283
AD  - Department of Cardiovascular Physiology, Faculty of Medicine, Kagawa University , 
      Kagawa , Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181219
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Calcium Channels, L-Type)
RN  - 0 (L-type calcium channel alpha(1C))
RN  - EC 2.7.11.1 (F2r protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 3.4.21.27 (Factor XIa)
RN  - EC 3.4.21.5 (Thrombin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blood Coagulation/physiology
MH  - Calcium/*metabolism
MH  - Calcium Channels, L-Type/metabolism
MH  - Cell Line
MH  - Cell Movement/*physiology
MH  - Factor XIa/*metabolism
MH  - Female
MH  - Kinetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Muscle, Smooth, Vascular/*metabolism
MH  - Myocytes, Smooth Muscle/*metabolism
MH  - Pregnancy
MH  - Protein Binding/physiology
MH  - Protein Serine-Threonine Kinases/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Thrombin/metabolism
OTO - NOTNLM
OT  - coagulation factor XI
OT  - proteinase-activated receptor
OT  - vascular smooth muscle
EDAT- 2018/12/20 06:00
MHDA- 2020/01/07 06:00
CRDT- 2018/12/20 06:00
PHST- 2018/12/20 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2018/12/20 06:00 [entrez]
AID - 10.1152/ajpcell.00426.2018 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2019 Mar 1;316(3):C377-C392. doi: 
      10.1152/ajpcell.00426.2018. Epub 2018 Dec 19.