Course of matrix metalloproteinase-9 isoforms after the administration of uric acid in patients with acute stroke: a proof-of-concept study.
Oxidative stress as well as expression and activity of matrix metalloproteinase 9 (MMP-9) are rapidly enhanced after cerebral ischemia. The magnitude of these effects is related to stroke outcome. In human stroke, the extent of oxidative stress correlates well with increased MMP-9 expression. The aim of this study was to evaluate whether treatment with the antioxidant molecule uric acid (UA) decreased the levels of MMP-9 in stroke patients treated with rtPA. The patients were part of a pilot, double-blind, randomized, vehicle-controlled study of patients with acute stroke treated with rtPA (< 3 h) and randomized to receive an intravenous infusion of UA (n = 16) or vehicle (n = 8). Total matrix metalloproteinase (tMMP)-9 and active (aMMP-9) levels were measured in serum at baseline (< 3 h), at the end of study treatment infusion (< 5.5 h), and at 48 hours. Total MMP-9 and aMMP-9 increased very early after stroke onset in patients allocated vehicle after rtPA therapy. Lower increments of aMMP-9 were associated with better outcome at 3 months. UA treatment was associated with reduced levels of aMMP-9 at T1 (p < 0.02) in multivariate models adjusted for age, NIHSS score, and baseline aMMP-9 levels. The decline of aMMP-9 attained after UA administration supports further clinical assessment of UA therapy in patients with acute stroke.
Amaro
Sergio
S
Stroke Unit, Institute of Neurosciences, Hospital Clínic, Villarroel, 170, 08036, Barcelona, Spain.
Obach
Víctor
V
Cervera
Alvaro
A
Urra
Xabier
X
Gómez-Choco
Manuel
M
Planas
Anna M
AM
Chamorro
Angel
A
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D015999:Multivariate Analysis; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010865:Pilot Projects; D020033:Protein Isoforms / Q000097:blood; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D020521:Stroke / Q000097:blood* / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D014527:Uric Acid / Q000008:administration & dosage*
D000975:Antioxidants; D018696:Neuroprotective Agents; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014527:Uric Acid; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9