Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase
SS Bolz, L Vogel, D Sollinger, R Derwand, C Boer… - Circulation, 2003 - Am Heart Assoc
Circulation, 2003•Am Heart Assoc
Background—RhoA and Rho kinase are important modulators of microvascular tone.
Methods and Results—We tested whether sphingosine kinase (Sphk1) that generates the
endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling
cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we
report that resting tone and myogenic responses of isolated resistance arteries increased
with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of …
Methods and Results—We tested whether sphingosine kinase (Sphk1) that generates the
endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling
cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we
report that resting tone and myogenic responses of isolated resistance arteries increased
with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of …
Background— RhoA and Rho kinase are important modulators of microvascular tone.
Methods and Results— We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses.
Conclusions— The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.
Am Heart Assoc