Angiotensin II-induced mitochondrial reactive oxygen species and peroxiredoxin-3 expression in cardiac fibroblasts

The aim of this study was to determine whether angiotensin II (ANG II) affects the protein and mRNA expression of the mitochondrial antioxidant peroxiredoxin-3 (Prx-3) in cardiac fibroblasts, thereby contributing to the oxidative stress in the myocardium.

Cardiac fibroblasts (passage 2) from normal male adult rats were cultured to confluency and incubated in Dulbecco's modified Eagle's medium for 24  h. The cells were then preincubated with(out) the tested inhibitors for 1  h and further incubated with/without ANG II (1 μmol/l) for 24  h.

ANG II increased (P < 0.001) the mitochondrial production of reactive oxygen species in cardiac fibroblasts from 187.8 ± 38.6 to 313.8 ± 30.6 a.u./mg mitochondrial protein (n = 15). ANG II decreased (P < 0.01) the mRNA and protein expression of Prx-3 by 36.9 ± 3.0% and 29.7 ± 2.7% (n = 4), respectively. The ANG II-induced decrease in mRNA expression of Prx-3 was prevented by the angiotensin type 1 receptor blocker, losartan but not by the angiotensin type 2 receptor blocker, PD 123 319.

Our data indicate that ANG II-stimulated mitochondrial reactive oxygen species production in rat cardiac fibroblasts is accompanied by a reduction in the expression of the mitochondrial antioxidant Prx-3, and thereby potentially contributing to oxidative stress in the myocard.