Liberation of vessel adherent myeloperoxidase by enoxaparin improves endothelial function.
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.


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).


CONCLUSIONS
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).
Rudolph
Tanja K
TK
Department of Cardiology and Angiology, Heart Center, University Hospital Hamburg-Eppendorf, Hamburg, 20246 Germany. t.rudolph@uke.uni-hamburg.de
Rudolph
Volker
V
Witte
Anna
A
Klinke
Anna
A
Szoecs
Katalin
K
Lau
Denise
D
Heitzer
Thomas
T
Meinertz
Thomas
T
Baldus
Stephan
S
D000368:Aged; D001682:Biological Availability; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology*; D017984:Enoxaparin / Q000494:pharmacology*; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000097:blood / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology
D008076:Cholesterol, HDL; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D009569:Nitric Oxide; D009195:Peroxidase