Interaction of myeloperoxidase with vascular NAD(P)H oxidase-derived reactive oxygen species in vasculature: implications for vascular diseases.
Vascular NAD(P)H oxidase-derived reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) have emerged as important molecules in the pathogenesis of atherosclerosis, hypertension, and diabetic vascular complications. Additionally, myeloperoxidase (MPO), a transcytosable heme protein that is derived from leukocytes, is also believed to play important roles in the above-mentioned inflammatory vascular diseases. Previous studies have shown that MPO-induced vascular injury responses are H2O2 dependent. It is well known that MPO can use leukocyte-derived H2O2; however, it is unknown whether the vascular-bound MPO can use vascular nonleukocyte oxidase-derived H2O2 to induce vascular injury. In the present study, ANG II was used to stimulate vascular NAD(P)H oxidases and increase their H2O2 production in the vascular wall, and vascular dysfunction was used as the vascular injury parameter. We demonstrated that vascular-bound MPO has sustained activity in the vasculature. MPO could use the vascular NAD(P)H oxidase-derived H2O2 to produce hypochlorus acid (HOCl) and its chlorinating species. More importantly, MPO derived HOCl and chlorinating species amplified the H2O2-induced vascular injury by additional impairment of endothelium-dependent relaxation. HOCl-modified low-density lipoprotein protein (LDL), a specific biomarker for the MPO-HOCl-chlorinating species pathway, was expressed in LDL and MPO-bound vessels with vascular NAD(P)H oxidase-derived H2O2. MPO-vascular NAD(P)H oxidase-HOCl-chlorinating species may represent a common pathogenic pathway in vascular diseases and a new mechanism involved in exacerbation of vascular diseases under inflammatory conditions.
Zhang
Chunxiang
C
Vascular Biology Center of Excellence, Department of Medicine, University of Tennessee Health Science Center, 956 Court Ave., Coleman Bldg., H300, Memphis, TN 38163, USA. czhang@utmem.edu
Yang
Jian
J
Jacobs
Jonathan D
JD
Jennings
Lisa K
LK
D000818:Animals; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D004730:Endothelium, Vascular / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism
D008078:Cholesterol, LDL; D017382:Reactive Oxygen Species; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; D019255:NADPH Oxidases