Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase | |
Article | |
关键词: SMOOTH-MUSCLE; RESISTANCE ARTERIES; RHO-KINASE; INTRACELLULAR SPHINGOSINE-1-PHOSPHATE; SIGNAL-TRANSDUCTION; CA2+; SENSITIVITY; 1-PHOSPHATE; PHOSPHATASE; EXPRESSION; | |
DOI : 10.1161/01.CIR.0000080324.12530.0D | |
来源: SCIE |
【 摘 要 】
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.
【 授权许可】
Free