Inverse relationship between markers of nitric oxide formation and plasma matrix metalloproteinase-9 levels in healthy volunteers.
BACKGROUND
Nitric oxide (NO) is a major regulator of cardiovascular homeostasis and has anti-atherogenic properties. Reduced NO formation is associated with endothelial dysfunction and with cardiovascular risk factors. Although NO downregulates the expression and activity of the pro-atherogenic enzyme matrix metalloproteinase-9 (MMP-9), no previous clinical study has examined whether endogenous NO formation is inversely associated with the circulating levels of pro-MMP-9, which are associated with cardiovascular events. We examined this hypothesis in 175 healthy male subjects who were non-smokers.


METHODS
To assess NO bioavailability, the plasma concentrations of nitrite, nitrate, and cGMP were determined using an ozone-based chemiluminescence assay and an enzyme immunoassay. Pro-MMP-9 and pro-MMP-2 levels were measured in plasma samples by gelatin zymography.


RESULTS
We found significant negative correlations between pro-MMP-9 levels and plasma nitrite (P=0.035, rs= -0.159), nitrate (P=0.040, rs= -0.158), and cGMP (P=0.011, rs= -0.189) concentrations. However, no significant correlations were found between pro-MMP-2 levels and the plasma concentrations of markers of NO bioavailability (all P>0.05).


CONCLUSIONS
There is an inverse relationship between markers of NO formation and plasma MMP-9 levels. This finding may shed some light on the possible mechanisms involved in the increased cardiovascular risk of apparently healthy subjects with low NO bioavailability or high circulating levels of pro-MMP-9.
Demacq
Caroline
C
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes 3900, Ribeirao Preto, SP, Brazil.
Metzger
Ingrid F
IF
Gerlach
Raquel F
RF
Tanus-Santos
Jose E
JE
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D006262:Health; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*
D015415:Biomarkers; D009569:Nitric Oxide; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9