TY - JOUR
T1 - Plasma matrix metalloproteinase and inhibitor profiles in patients with heart failure
AU - Wilson, Eric M.
AU - Gunasinghe, Himali R.
AU - Coker, Mytsi L.
AU - Sprunger, Philip
AU - Lee-Jackson, Dorellyn
AU - Bozkurt, Biykem
AU - Deswal, Anita
AU - Mann, Douglas L.
AU - Spinale, Francis G.
N1 - Funding Information:
This study was supported in part by NIH grants HL59165-05, HL61543, and HL58081.
PY - 2002/12
Y1 - 2002/12
N2 - 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)-α can induce MMP expression in vitro. The second objective of this study was to determine the relationship between soluble TNF-α receptors (TNFR1; TNFR2) and MMP plasma profiles. Methods and Results: Plasma levels of MMP-2, MMP-9, MMP-8, TIMP-1, TIMP-2, TNF-α 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/mLP = .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.
AB - 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)-α can induce MMP expression in vitro. The second objective of this study was to determine the relationship between soluble TNF-α receptors (TNFR1; TNFR2) and MMP plasma profiles. Methods and Results: Plasma levels of MMP-2, MMP-9, MMP-8, TIMP-1, TIMP-2, TNF-α 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/mLP = .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.
KW - Cytokines
KW - Heart failure
KW - Matrix metalloproteinases
KW - TIMPs
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UR - http://www.scopus.com/inward/citedby.url?scp=0036940681&partnerID=8YFLogxK
U2 - 10.1054/jcaf.2002.129659
DO - 10.1054/jcaf.2002.129659
M3 - Article
C2 - 12528092
AN - SCOPUS:0036940681
SN - 1071-9164
VL - 8
SP - 390
EP - 398
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 6
ER -