Natural History of Markers of Collagen Turnover in Patients With Early Diastolic Dysfunction and Impact of Eplerenone.

Mak, G.J., Ledwidge, M.T., Watson, C.J., Phelan, D.M., Dawkins, I.R., Murphy, N.F., Patle, A.K., Baugh, J.A., McDonald, K.M.
Journal   J Am Coll Cardiol.
Species  
Analytes Measured   CRP , IL-6 , IL-8 , MCP-1
Matrix Tested   Serum
Year   2009
Volume   54
Page Numbers   1674-82
Application   Cytokines and Chemokines
Abstract
OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF). BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

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Multiplex
U-PLEX Biomarker Group 1 (hu) Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Custom Biomarker Group 1 Human Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, EPO, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-β, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-2Rα, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17E/IL-25, IL-17F, IL-18, IL-21, IL-22, IL-23, IL-27, IL-29/IFN-λ1, IL-31, IL-33, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, TSLP, VEGF-A, YKL-40 | Human
Multiplex
U-PLEX Proinflam Combo 1 (NHP)
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12/IL-23p40, TNF-α | Non-human primate
Multiplex
U-PLEX Biomarker Group 1 (NHP) Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX Custom Biomarker Group 1 (NHP) Assays
CTACK, ENA-78, Eotaxin, Eotaxin-2, Eotaxin-3, FLT3L, Fractalkine, G-CSF, GM-CSF, GRO-α, I-309, IFN-α2a, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IL-17A/F, IL-17B, IL-17C, IL-17D, IL-17F, IL-18, IL-22, IL-23, IP-10, I-TAC, MCP-1, MCP-2, MCP-3, MCP-4, M-CSF, MDC, MIF, MIP-1α, MIP-1β, MIP-3α, MIP-3β, MIP-5, SDF-1α, TARC, TGF-β1, TGF-β2, TGF-β3, TNF-α, TNF-β, TPO, TRAIL, VEGF-A, YKL-40 | Non-human primate
Multiplex
U-PLEX TH1/TH2 Combo (hu)
IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
U-PLEX Proinflam Combo 3 (hu)
IFN-γ, IL-1β, IL-6, TNF-α | Human
Multiplex
U-PLEX Proinflam Combo 1 (hu)
IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α | Human
Multiplex
U-PLEX Chemokine Combo 1 (NHP)
Eotaxin, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
U-PLEX Proinflam Combo 4 (hu)
IL-1β, IL-6, IL-8, TNF-α | Human
Multiplex
U-PLEX Chemokine Combo 1 (hu)
Eotaxin, Eotaxin-2, Eotaxin-3, IL-8, IP-10, MCP-1, MCP-2, MCP-3, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Human
Multiplex
U-PLEX Human MCP-1 Antibody Set
MCP-1 | Human
U-PLEX Human IL-6 Antibody Set
IL-6 | Human
U-PLEX Human IL-8 Antibody Set
IL-8 | Human
U-PLEX Mouse IL-6 Antibody Set
IL-6 | Mouse
V-PLEX Plus Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
V-PLEX Proinflammatory Panel 2 Rat Kit
IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO, TNF-α | Rat
Multiplex
V-PLEX Human Biomarker 40-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Plus Human Biomarker 40-Plex Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), GM-CSF, ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-12p70, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
V-PLEX Vascular Injury Panel 2 Human Kit
CRP, ICAM-1, SAA, VCAM-1 | Human
Multiplex
V-PLEX Plus Vascular Injury Panel 2 Human Kit
CRP, ICAM-1, SAA, VCAM-1 | Human
Multiplex
V-PLEX NHP IL-8 Kit
IL-8 | Non-human primate
Singleplex
V-PLEX NHP IL-6 Kit
IL-6 | Non-human primate
Singleplex
V-PLEX NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Plus NHP Cytokine 24-Plex Kit
Eotaxin-3, GM-CSF, IFN-γ, IL-1β, IL-2, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, IL-12/IL-23p40, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-β, VEGF-A | Non-human primate
Multiplex
V-PLEX Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Proinflammatory Panel 1 NHP Kit
IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10 | Non-human primate
Multiplex
V-PLEX Plus Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Chemokine Panel 1 NHP Kit
Eotaxin-3, IL-8, IL-8 (HA), IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC | Non-human primate
Multiplex
V-PLEX Plus Neuroinflammation Panel 1 Human Kit
CRP, Eotaxin, Eotaxin-3, FGF (basic), ICAM-1, IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, PlGF, SAA, TARC, Tie-2, TNF-α, TNF-β, VCAM-1, VEGF-A, VEGF-C, VEGF-D, VEGFR-1/Flt-1 | Human
Multiplex
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