Increased circulating levels of matrix metalloproteinase (MMP)-8, MMP-9, and pro-inflammatory markers in patients with metabolic syndrome.
BACKGROUND
Metabolic syndrome (MetS) predisposes to cardiovascular complications. Increased concentrations of pro-inflammatory mediators and imbalanced concentrations of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) may reflect the pathophysiology of MetS. We compared the circulating levels of MMPs, TIMPs, and inflammatory mediators in MetS patients with those found in healthy controls.


METHODS
We studied 25 healthy subjects and 25 MetS patients. The plasma levels of pro-MMP-2 and pro-MMP-9 were determined by gelatin zymography. The plasma concentrations of MMP-8, MMP-3, TIMP-1, TIMP-2, monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule (sICAM-1), and sP-selectin were measured by ELISA kits.


RESULTS
We found higher sP-selectin, sICAM-1, MCP-1, and IL-6 (all P<0.05) concentrations in MetS patients compared with healthy controls. No differences in pro-MMP-2, MMP-3, and TIMP-2 levels were found (all P>0.05). However, we found higher pro-MMP-9, MMP-8, and TIMP-1 levels in MetS patients compared with healthy controls (all P<0.05).


CONCLUSIONS
Patients with MetS have increased circulating concentrations of pro-MMP-9, MMP-8, and TIMP-1 that are associated with increased concentrations of pro-inflammatory mediators and adhesion molecules. These findings suggest that MMPs may have a role in the increased cardiovascular risk of MetS patients. Pharmacological interventions targeting MMPs, especially MMP-9 and MMP-8 deserve further investigation in MetS patients.
Gonçalves
Flavia M
FM
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, SP, Brazil.
Jacob-Ferreira
Anna L B
AL
Gomes
Valeria A
VA
Casella-Filho
Antonio
A
Chagas
Antonio C P
AC
Marcaccini
Andrea M
AM
Gerlach
Raquel F
RF
Tanus-Santos
Jose E
JE
D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000097:blood* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000097:blood* / Q000378:metabolism; D024821:Metabolic Syndrome / Q000097:blood* / Q000378:metabolism; D008875:Middle Aged; D019087:Selectins / Q000097:blood / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood / Q000378:metabolism
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D019087:Selectins; D019715:Tissue Inhibitor of Metalloproteinase-1; D018799:Intercellular Adhesion Molecule-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9