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】

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