Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function
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Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function. / Rudolph, Tanja K; Rudolph, Volker; Witte, Anna; Klinke, Anna; Szoecs, Katalin; Lau, Denise; Heitzer, Thomas; Meinertz, Thomas; Baldus, Stephan.
in: INT J CARDIOL, Jahrgang 140, Nr. 1, 01.04.2010, S. 42-47.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function
AU - Rudolph, Tanja K
AU - Rudolph, Volker
AU - Witte, Anna
AU - Klinke, Anna
AU - Szoecs, Katalin
AU - Lau, Denise
AU - Heitzer, Thomas
AU - Meinertz, Thomas
AU - Baldus, Stephan
N1 - Copyright 2008 Elsevier Ireland Ltd. All rights reserved.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - BACKGROUND: Myeloperoxidase (MPO), a leukocyte-derived heme enzyme binds to the endothelium and depletes vascular nitric oxide (NO) bioavailability in animal models. Unfractionated heparins release vessel-bound MPO and increase endothelial NO bioavailability. Whether low molecular weight heparins also affect circulating MPO levels and NO dependent vasoreactivity however remains elusive.METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial patients with stable coronary artery disease received either 1 mg/kg enoxaparin or an equivalent volume of sodium chloride (NaCl) subcutaneously. Enoxaparin led to a significant improvement of FMD (5.51+/-0.53% vs. 6.55+/-0.58%, p=0.01) accompanied by a significant increase in plasma MPO levels (2.51 [IR: 2.04-3.62] ng/ml vs. 3.70 [IR: 2.80-5.50] ng/ml; p<0.001) whereas NaCl revealed neither a change in FMD (5.56+/-0.67% vs. 5.34+/-0.61%, p=ns) nor in plasma MPO levels (3.04 [IR: 2.22-4.67] ng/ml vs. 2.90 [IR: 1.95-4.32] ng/ml; p=ns). The extent of enoxaparin-induced MPO release and the improvement in endothelial function showed a good correlation (r=0.67, p<0.001).DISCUSSION: This study confirms the concept that heparins improve endothelial function, an established read-out of vascular NO bioavailability, by mobilizing vessel bound MPO. These data not only support the notion of extracoagulant, anti-inflammatory properties of heparins but reinforce the concept of MPO-dependent NO oxidation as a central mechanism for regulation of vascular tone in inflammatory vascular disease. (Eudra-CT number: 2005-006113-40).
AB - BACKGROUND: Myeloperoxidase (MPO), a leukocyte-derived heme enzyme binds to the endothelium and depletes vascular nitric oxide (NO) bioavailability in animal models. Unfractionated heparins release vessel-bound MPO and increase endothelial NO bioavailability. Whether low molecular weight heparins also affect circulating MPO levels and NO dependent vasoreactivity however remains elusive.METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial patients with stable coronary artery disease received either 1 mg/kg enoxaparin or an equivalent volume of sodium chloride (NaCl) subcutaneously. Enoxaparin led to a significant improvement of FMD (5.51+/-0.53% vs. 6.55+/-0.58%, p=0.01) accompanied by a significant increase in plasma MPO levels (2.51 [IR: 2.04-3.62] ng/ml vs. 3.70 [IR: 2.80-5.50] ng/ml; p<0.001) whereas NaCl revealed neither a change in FMD (5.56+/-0.67% vs. 5.34+/-0.61%, p=ns) nor in plasma MPO levels (3.04 [IR: 2.22-4.67] ng/ml vs. 2.90 [IR: 1.95-4.32] ng/ml; p=ns). The extent of enoxaparin-induced MPO release and the improvement in endothelial function showed a good correlation (r=0.67, p<0.001).DISCUSSION: This study confirms the concept that heparins improve endothelial function, an established read-out of vascular NO bioavailability, by mobilizing vessel bound MPO. These data not only support the notion of extracoagulant, anti-inflammatory properties of heparins but reinforce the concept of MPO-dependent NO oxidation as a central mechanism for regulation of vascular tone in inflammatory vascular disease. (Eudra-CT number: 2005-006113-40).
KW - Aged
KW - Biological Availability
KW - Cholesterol, HDL/blood
KW - Coronary Artery Disease/physiopathology
KW - Double-Blind Method
KW - Endothelium, Vascular/drug effects
KW - Enoxaparin/pharmacology
KW - Female
KW - Fibrinolytic Agents/pharmacology
KW - Humans
KW - Male
KW - Middle Aged
KW - Nitric Oxide/metabolism
KW - Peroxidase/blood
KW - Regional Blood Flow/drug effects
U2 - 10.1016/j.ijcard.2008.10.035
DO - 10.1016/j.ijcard.2008.10.035
M3 - SCORING: Journal article
C2 - 19049846
VL - 140
SP - 42
EP - 47
JO - INT J CARDIOL
JF - INT J CARDIOL
SN - 0167-5273
IS - 1
ER -