Plasma matrix metalloproteinase and inhibitor profiles in patients with heart failure.
BACKGROUND
Changes in myocardial matrix metalloproteinases (MMPs) and the inhibitors of MMPs (TIMPs) have been demonstrated in congestive heart failure (CHF). The first objective of this study was to measure plasma profiles of MMPs and TIMPs in CHF patients (n = 24; 62 +/- 3 years; left ventricular ejection fraction [LVEF] = 24 +/- 2%) and age-matched nonfailing patients (n = 48; 63 +/- 2 years; LVEF >/= 55%). Cytokines such as tumor necrosis factor (TNF)-alpha can induce MMP expression in vitro. The second objective of this study was to determine the relationship between soluble TNF-alpha receptors (TNFR1; TNFR2) and MMP plasma profiles.


RESULTS
Plasma levels of MMP-2, MMP-9, MMP-8, TIMP-1, TIMP-2, TNF-alpha, TNFR1, and TNFR2 were measured by enzyme-linked immunosorbent assay kits. Plasma MMP-9 levels were increased in CHF patients (25 +/- 6 versus 72 +/- 15 ng/mL, P <.05). Interestingly, plasma levels of MMP-8 were decreased in CHF patients (16 +/- 2 versus 9 +/- 2 ng/mL, P <.05). The MMP-9/TIMP-1 ratio was increased by 3-fold, whereas the MMP-9/TIMP-2 ratio was increased by 16-fold in CHF patients (both P <.05). With a 48-week follow-up in CHF patients, an absolute reduction in plasma TNFR1 from baseline was accompanied by reduced MMP-9 levels (-30 +/- 16 ng/mL; P =.058), whereas stable or increased plasma TNFR1 resulted in persistently elevated MMP-9 levels.


CONCLUSIONS
The unique findings of this study were 2-fold. First, a discordant change in plasma MMP and TIMP levels occurred in CHF patients. Second, changes in cytokine activity were related to changes in plasma MMP levels. These changes in MMP/TIMP levels likely reflect the progression and/or acceleration of the LV remodeling process in CHF. Thus serial measurements of plasma MMP/TIMP levels may hold diagnostic/prognostic significance in CHF patients.
Wilson
Eric M
EM
Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Gunasinghe
Himali R
HR
Coker
Mytsi L
ML
Sprunger
Philip
P
Lee-Jackson
Dorellyn
D
Bozkurt
Biykem
B
Deswal
Anita
A
Mann
Douglas L
DL
Spinale
Francis G
FG
D000368:Aged; D015415:Biomarkers / Q000097:blood; D004789:Enzyme Activation / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood* / Q000276:immunology; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000276:immunology; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood* / Q000276:immunology
D015415:Biomarkers; D018124:Receptors, Tumor Necrosis Factor; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases