Heparins Increase Endothelial Nitric Oxide Bioavailability by Liberating Vessel-Immobilized Myeloperoxidase

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-04, Vol.113 (15), p.1871-1878
• Main Authors: BALDUS, Stephan, RUDOLPH, Volker, KUBALA, Lukas, BERGLUND, Lars, SCHREPFER, Sonja, DEUSE, Tobias, HADDAD, Munif, RISIUS, Tim, KLEMM, Hanno, REICHENSPURNER, Hermann C, MEINERTZ, Thomas, HEITZER, Thomas, ROISS, Mika, ITO, Wulf D, RUDOLPH, Tanja K, EISERICH, Jason P, SYDOW, Karsten, LAU, Denise, SZOCS, Katalin, KLINKE, Anna
• Format: Article
• Language: English
• Subjects: Aged; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Biological Availability; Blood and lymphatic vessels; Blood Vessels - drug effects; Blood Vessels - enzymology; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Case-Control Studies; Cells, Cultured; Coronary heart disease; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Female; Heart; Heparin - pharmacology; Humans; In Vitro Techniques; Male; Medical sciences; Middle Aged; Nitric Oxide - metabolism; Pancreatic Elastase - blood; Peroxidase - blood; Peroxidase - metabolism; Pharmacology. Drug treatments
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.105.590083

Neutrophils and monocytes are centrally linked to vascular inflammatory disease, and leukocyte-derived myeloperoxidase (MPO) has emerged as an important mechanistic participant in impaired vasomotor function. MPO binds to and transcytoses endothelial cells in a glycosaminoglycan-dependent manner, and MPO binding to the vessel wall is a prerequisite for MPO-dependent oxidation of endothelium-derived nitric oxide (NO) and impairment of endothelial function in animal models. In the present study, we investigated whether heparin mobilizes MPO from vascular compartments in humans and defined whether this translates into increased vascular NO bioavailability and function. Plasma MPO levels before and after heparin administration were assessed by ELISA in 109 patients undergoing coronary angiography. Whereas baseline plasma MPO levels did not differ between patients with or without angiographically detectable coronary artery disease (CAD), the increase in MPO plasma content on bolus heparin administration was higher in patients with CAD (P=0.01). Heparin treatment also improved endothelial NO bioavailability, as evidenced by flow-mediated dilation (P