Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function

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 -