|Pathophysiology of venous abnormalities in multiple sclerosis and potential therapeutic strategies|
|Pathophysiology||Involved molecules||Potential intervention||Potential treatments||References|
|Higher venous endothelial responses to inflammation||Cytokines, chemokines, adhesion molecules, occludin||Induction of MKP-1, protection against shear stress responses||Dexamethasone||[16,39]|
|Altered hemodynamic signaling in venous inflammation||KLF2, KLF4, eNOS, VCAM-1, PAI-I, TNF-α||Activation of KLF2 and KLF4||Statin drugs, HDAC inhibitors (for example, trichostatin-A)||[8,30,36,40]|
|BBB dysregulation||NMDA receptor, MMP-8, MMP-9, p38 MAPK||MMP inhibitor, p38 MAPK inhibitor||Doxycycline, minocycline, SB 239063||[41-44]|
|Venous remodeling||Collagens, iron, TGF-β1, p38 MAPK, VEGF, TIMP, MMP||p38 MAPK inhibitor, TGF modifier, angiotensin antagonist, anti-angiogenic drug, MMP inhibitor||Drugs (dilamapimod, avotermin, candesartan, bevacizumab, cavtratin, doxycycline, desferrioxamine)||[8,45-47]|
|Hemodynamic abnormality, CCSVI||PGI2, NO, EDHF||Venous pressure reduction||venoplasty||[48,49]|
Abbreviations:BBB blood-brain barrier, CCSVI chronic cerebrospinal venous insufficiency, EDHF endothelium-derived hyperpolarizing factor, eNOS Endothelial nitric oxide synthase, HDAC histone deacetylase, KLF Krueppel-like factor, MAPK mitogen-activated protein kinase, MKP mitogen-activated protein kinase phosphatase, MMP matrix metalloproteinase, MS multiple sclerosis, NMDA N-methyl-D-aspartate, NO nitrous oxide, PAI plasminogen activator inhibitor, PGI2 prostaglandin I2 (prostacyclin), TGF transforming growth factor, TIMP tissue inhibitor of metalloproteinase, TNF tumor necrosis factor, VCAM vascular cell adhesion molecule, VEGF Vascular endothelial growth factor.
Alexander et al.
Alexander et al. BMC Medicine 2013 11:219 doi:10.1186/1741-7015-11-219