PMID- 25208915
OWN - NLM
STAT- MEDLINE
DCOM- 20160414
LR  - 20211203
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 467
IP  - 8
DP  - 2015 Aug
TI  - Kv1.3 channels modulate human vascular smooth muscle cells proliferation 
      independently of mTOR signaling pathway.
PG  - 1711-22
LID - 10.1007/s00424-014-1607-y [doi]
AB  - Phenotypic modulation (PM) of vascular smooth muscle cells (VSMCs) is central to 
      the process of intimal hyperplasia which constitutes a common pathological lesion 
      in occlusive vascular diseases. Changes in the functional expression of Kv1.5 and 
      Kv1.3 currents upon PM in mice VSMCs have been found to contribute to cell 
      migration and proliferation. Using human VSMCs from vessels in which unwanted 
      remodeling is a relevant clinical complication, we explored the contribution of 
      the Kv1.5 to Kv1.3 switch to PM. Changes in the expression and the functional 
      contribution of Kv1.3 and Kv1.5 channels were studied in contractile and 
      proliferating VSMCs obtained from human donors. Both a Kv1.5 to Kv1.3 switch upon 
      PM and an anti-proliferative effect of Kv1.3 blockers on PDGF-induced 
      proliferation were observed in all vascular beds studied. When investigating the 
      signaling pathways modulated by the blockade of Kv1.3 channels, we found that 
      anti-proliferative effects of Kv1.3 blockers on human coronary artery VSMCs were 
      occluded by selective inhibition of MEK/ERK and PLCgamma signaling pathways, but were 
      unaffected upon blockade of PI3K/mTOR pathway. The temporal course of the 
      anti-proliferative effects of Kv1.3 blockers indicates that they have a role in 
      the late signaling events essential for the mitogenic response to growth factors. 
      These findings establish the involvement of Kv1.3 channels in the PM of human 
      VSMCs. Moreover, as current therapies to prevent restenosis rely on mTOR 
      blockers, our results provide the basis for the development of novel, more 
      specific therapies.
FAU - Cidad, Pilar
AU  - Cidad P
AD  - Departamento de Bioquimica y Biologia Molecular y Fisiologia e Instituto de 
      Biologia y Genetica Molecular (IBGM), Universidad de Valladolid y CSIC, Edificio 
      IBGM, c/ Sanz y Fores s/n, 47003, Valladolid, Spain.
FAU - Miguel-Velado, Eduardo
AU  - Miguel-Velado E
FAU - Ruiz-McDavitt, Christian
AU  - Ruiz-McDavitt C
FAU - Alonso, Esperanza
AU  - Alonso E
FAU - Jimenez-Perez, Laura
AU  - Jimenez-Perez L
FAU - Asuaje, Agustin
AU  - Asuaje A
FAU - Carmona, Yamila
AU  - Carmona Y
FAU - Garcia-Arribas, Daniel
AU  - Garcia-Arribas D
FAU - Lopez, Javier
AU  - Lopez J
FAU - Marroquin, Yngrid
AU  - Marroquin Y
FAU - Fernandez, Mirella
AU  - Fernandez M
FAU - Roque, Merce
AU  - Roque M
FAU - Perez-Garcia, M Teresa
AU  - Perez-Garcia MT
FAU - Lopez-Lopez, Jose Ramon
AU  - Lopez-Lopez JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140912
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (KCNA3 protein, human)
RN  - 0 (KCNA5 protein, human)
RN  - 0 (Kv1.3 Potassium Channel)
RN  - 0 (Kv1.5 Potassium Channel)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Potassium Channel Blockers)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Cell Proliferation/drug effects
MH  - Cells, Cultured
MH  - Humans
MH  - Kv1.3 Potassium Channel/antagonists & inhibitors/genetics/metabolism
MH  - Kv1.5 Potassium Channel/genetics/metabolism
MH  - Membrane Potentials
MH  - Muscle, Smooth, Vascular/drug effects/*enzymology
MH  - Myocytes, Smooth Muscle/drug effects/*enzymology
MH  - Phenotype
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Potassium Channel Blockers/pharmacology
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA, Messenger/metabolism
MH  - *Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
MH  - Time Factors
EDAT- 2014/09/12 06:00
MHDA- 2016/04/15 06:00
CRDT- 2014/09/12 06:00
PHST- 2014/06/23 00:00 [received]
PHST- 2014/09/01 00:00 [accepted]
PHST- 2014/08/07 00:00 [revised]
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2016/04/15 06:00 [medline]
AID - 10.1007/s00424-014-1607-y [doi]
PST - ppublish
SO  - Pflugers Arch. 2015 Aug;467(8):1711-22. doi: 10.1007/s00424-014-1607-y. Epub 2014 
      Sep 12.