Sphingosine 1-Phosphate as a Therapeutic Target in Heart Failure: More Questions than Answers
Sphingosine-1-phosphate (S1P) is a naturally occurring bioactive lysophospholipid that regulates immune responses and inflammatory processes in a variety of different organ systems, including the cardiovascular system. Within the cardiovascular system S1P mediates cardioprotection following ischemia/reperfusion injury, cardiac remodeling, vascular tone, angiogenesis, as well as fibroblast migration, proliferation, and differentiation1. In the current issue of Circulation, Meissner and colleagues present novel findings in a murine heart failure model (LAD ligation) which suggest that S1P activity is modulated by a cAMP-responsive chloride channel termed the cystic fibrosis transmembrane regulator (CFTR).2 CFTR, a member of the ATP binding cassette family of genes, was identified as the gene responsible for the loss of chloride secretion in patients with cystic fibrosis. Based on a prior report by the same group,3 which showed that the intracellular enzyme S1P phosphohydrolase that degrades extracellular S1P, was also an endogenous regulator of S1P mediated vasoconstriction, the authors hypothesized that S1P must be imported by vascular smooth muscle cells. (SELECT FULL TEXT TO CONTINUE)
- Received April 14, 2012.
- Accepted April 17, 2012.
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