AI Article Synopsis
- RhoA and Rho kinase are key players in regulating microvascular tone, which is important for blood flow control.
- Researchers found that overexpressing sphingosine kinase 1 (Sphk1) in smooth muscle cells boosted the resting tone and myogenic responses in resistance arteries.
- The study concludes that Sphk1's ability to increase vascular tone indicates it may significantly influence peripheral resistance control in the body.
Article Abstract
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.
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| http://dx.doi.org/10.1161/01.CIR.0000080324.12530.0D | DOI Listing |
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