TY - JOUR
T1 - Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase
AU - Morgan, P E
AU - Laura, R P
AU - Maki, R A
AU - Reynolds, W F
AU - Davies, Michael Jonathan
PY - 2015/6/1
Y1 - 2015/6/1
N2 - 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.
AB - 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.
U2 - 10.3109/10715762.2015.1019347
DO - 10.3109/10715762.2015.1019347
M3 - Journal article
C2 - 25812586
SN - 1071-5762
VL - 49
SP - 743
EP - 749
JO - Free Radical Research
JF - Free Radical Research
IS - 6
ER -