title: Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase.
abstract: Elevated levels of the heme enzyme myeloperoxidase (MPO) are associated with adverse cardiovascular outcomes. MPO predominantly catalyzes formation of the oxidants hypochlorous acid (HOCl) from Cl(-), and hypothiocyanous acid (HOSCN) from SCN(-), with these anions acting as competitive substrates. HOSCN is a less powerful and more specific oxidant than HOCl, and selectively targets thiols; such damage is largely reversible, unlike much HOCl-induced damage. We hypothesized that increased plasma SCN(-), and hence HOSCN formation instead of HOCl, may decrease artery wall damage. This was examined using high-fat fed atherosclerosis-prone LDLR(-/-) mice transgenic for human MPO, with and without SCN(-) (10 mM) added to drinking water. Serum samples, collected fortnightly, were analyzed for cholesterol, triglycerides, thiols, MPO, and SCN(-); study-long exposure was calculated by area under the curve (AUC). Mean serum SCN(-) concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (< 120 μM). Normalized aortic root plaque areas at sacrifice were 26% lower in the SCN(-)-supplemented mice compared with controls (P = 0.0417), but plaque morphology was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN(-)-supplemented versus control mice showed no significant changes in MPO protein, cholesterol, or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque areas increased with higher cholesterol AUC (r = 0.4742; P = 0.0468), and decreased with increasing SCN(-) AUC (r = - 0.5693; P = 0.0134). These data suggest that increased serum SCN(-) levels, which can be achieved in humans by dietary manipulation, may decrease atherosclerosis burden.
authors: The Heart Research Institute , Newtown, NSW , Australia.
authors: P E
authors: PE
authors: Morgan
authors: R P
authors: RP
authors: Laura
authors: R A
authors: RA
authors: Maki
authors: W F
authors: WF
authors: Reynolds
authors: M J
authors: MJ
authors: Davies
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D019587:Dietary Supplements; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009195:Peroxidase / Q000235:genetics*; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000201:enzymology; D013861:Thiocyanates / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D013861:Thiocyanates; D009195:Peroxidase; C031760:thiocyanate
keywords: atherosclerosis; hypochlorous acid; hypothiocyanous acid; myeloperoxidase; thiocyanate; thiol oxidation