title: Myeloperoxidase deficiency preserves vasomotor function in humans.
abstract: OBJECTIVE
  Observational studies have suggested a mechanistic link between the leucocyte-derived enzyme myeloperoxidase (MPO) and vasomotor function. Here, we tested whether MPO is systemically affecting vascular tone in humans.
  
  
  RESULTS
  A total of 12 135 patients were screened for leucocyte peroxidase activity. We identified 15 individuals with low MPO expression and activity (MPO(low)), who were matched with 30 participants exhibiting normal MPO protein content and activity (control). Nicotine-dependent activation of leucocytes caused attenuation of endothelial nitric oxide (NO) bioavailability in the control group (P < 0.01), but not in MPO(low) individuals (P = 0.12); here the MPO burden of leucocytes correlated with the degree of vasomotor dysfunction (P = 0.008). To directly test the vasoactive properties of free circulating MPO, the enzyme was injected into the left atrium of anaesthetized, open-chest pigs. Myeloperoxidase plasma levels peaked within minutes and rapidly declined thereafter, reflecting vascular binding of MPO. Blood flow in the left anterior descending artery and the internal mammary artery (IMA) as well as myocardial perfusion decreased following MPO injection when compared with albumin-treated animals (P < 0.001). Isolated IMA-rings from animals subjected to MPO revealed markedly diminished relaxation in response to acetylcholine (P < 0.01) and nitroglycerine as opposed to controls (P < 0.001).
  
  
  CONCLUSIONS
  Myeloperoxidase elicits profound effects on vascular tone of conductance and resistance vessels in vivo. These findings not only call for revisiting the biological functions of leucocytes as systemic and mobile effectors of vascular tone, but also identify MPO as a critical systemic regulator of vasomotion in humans and thus a potential therapeutic target.
authors: Cardiovascular Research Center and Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. t.rudolph@uke.de
authors: Tanja K
authors: TK
authors: Rudolph
authors: Sabine
authors: S
authors: Wipper
authors: Beate
authors: B
authors: Reiter
authors: Volker
authors: V
authors: Rudolph
authors: Anja
authors: A
authors: Coym
authors: Christian
authors: C
authors: Detter
authors: Denise
authors: D
authors: Lau
authors: Anna
authors: A
authors: Klinke
authors: Kai
authors: K
authors: Friedrichs
authors: Thomas
authors: T
authors: Rau
authors: Michaela
authors: M
authors: Pekarova
authors: Detlef
authors: D
authors: Russ
authors: Kay
authors: K
authors: Knöll
authors: Mandy
authors: M
authors: Kolk
authors: Bernd
authors: B
authors: Schroeder
authors: Karl
authors: K
authors: Wegscheider
authors: Hilke
authors: H
authors: Andresen
authors: Edzard
authors: E
authors: Schwedhelm
authors: Rainer
authors: R
authors: Boeger
authors: Heimo
authors: H
authors: Ehmke
authors: Stephan
authors: S
authors: Baldus
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001783:Blood Flow Velocity; D003326:Coronary Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000201:enzymology; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D018375:Neutrophil Activation; D009504:Neutrophils / Q000201:enzymology*; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D034421:Sus scrofa; D014664:Vasodilation / Q000502:physiology; D014666:Vasomotor System / Q000201:enzymology*; D055815:Young Adult
chemical_list: D009569:Nitric Oxide; D009538:Nicotine; D009195:Peroxidase; D020780:Matrix Metalloproteinase 9