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Recent research indicates that sphingosine-1-phosphate (S1P) signaling is an important regulator of vascular smooth muscle contraction. When transmural pressure increases, sphingosine kinase 1 phosphorylates sphingosine to S1P, which binds to the S1P2 receptor in plasma membrane of cells. This leads to a transient increase in intracellular calcium, and activates Rac and Rhoa signaling pathways. Collectively, these serve to increase MLCK activity and decrease MLCP activity, promoting muscle contraction. This allows arterioles to increase resistance in response to increased blood pressure and thus maintain constant blood flow. The Rhoa and Rac portion of the signaling pathway provides a calcium-independent way to regulate resistance artery tone.

Although S1P is of importance in the entire human body, it is a major regulator of vascular and immune systems.... In the vascular system, S1P regulates angiogenesis, vascular stability, and permeability. In the immune system, it is now recognized as a major regulator of trafficking of T- and B-cells. S1P interaction with its receptor S1PR1 is needed for the egress of immune cells from the lymphoid organs (such as thymus and lymph nodes) into the lymphatic vessels. Inhibition of S1P receptors was shown to be critical for immunomodulation.

Interesting that something found to be effective on MS, also affects the smooth muscle's found in veins.

Fingolimod targets sphingosine 1-phosphate (S1P) receptors, of which the mRNA is widely expressed in immune, vascular and neural cells. The expression levels of the five S1P receptor subtypes in cell membranes versus cytoplasmic compartments may vary considerably depending on the activation and differentiation stage of the cells and the tissue levels of the ligand S1P48. Relevant targets of fingolimod may include cell membrane-expressed S1P1 on T and B cells38, 55, S1P1 and S1P3 on astrocytes114, 115 and, perhaps, S1P1 on neurons102, S1P1 and S1P5 on oligodendrocytes (OGCs)101, 109, and S1P1 on endothelial cells of the blood–brain barrier48. S1P receptors modulate the actin cytoskeleton of cells, thereby affecting pseudopodia formation and migration of lymphocytes, process outgrowth and retraction in neural cells, junctional communication between those cells, endothelial cell migration, and angiogenesis and endothelial permeability barriers48. IFN, interferon; IL, interleukin; MHC class II, major histocompatibility complex class II; MMPs, matrix metalloproteinases; NO, nitric oxide; TGFβ, transforming growth factor-β; TNF, tumour necrosis factor.

Interesting find, Cure!

Researchers can only posit what Fingolimod is actually affecting....notice how they say "targets may include" because S1P receptors are endothelial receptors. S1P maintains endothelial integrity.

This drug has many side effects. I'd stay clear of it.

There are much safer and cheaper ways to increase nitric oxide and help strengthen the endothelium.
http://www.ccsvi.org/index.php/helping- ... ial-health

Do users report heat sensitivity decreases?

... then those with CCSVI would need all of the lymphocytes...

LDN seems a much more appropriate drug treatment post venoplasty to me.

MegansMom wrote:
LDN seems a much more appropriate drug treatment post venoplasty to me.
Admittedly before venoplasty, but LDN did nothing for me.

Given these observations of S1P and FTY720, we explored the barrier-regulatory capacity of several novel, synthetic analogues of FTY720. We now demonstrate the similar, but not identical, barrier-regulatory mechanisms of these analogues to S1P and FTY720, with one class of analogues producing significant barrier disruption despite structural similarities. Finally, our in vivo data demonstrate that the representative (S)-phosphonate analogue of FTY720 significantly reduces LPS-induced vascular leak in a murine model of inflammatory lung injury. These studies advance our understanding of pulmonary vascular permeability and characterize four novel FTY720 analogues that may potentially act as improved therapeutic tools for prevention and reversal of vascular leak.