Hypertension and Cardiovascular Rehabilitation Unit, Department of Cardiovascular Sciences, Catholic University of Leuven (KULeuven), Leuven, Belgium.
J Hypertens. 2012 Oct;30(10):1986-91. doi: 10.1097/HJH.0b013e32835726c1.
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.
本研究旨在确定血管紧张素 II（ANG II）是否影响心肌成纤维细胞中线粒体抗氧化剂过氧化物酶 3（Prx-3）的蛋白和 mRNA 表达，从而导致心肌的氧化应激。
培养正常雄性成年大鼠的心肌成纤维细胞（第 2 代）至汇合状态，并在 Dulbecco 改良 Eagle 培养基中孵育 24 小时。然后，将细胞用（不用）测试抑制剂预孵育 1 小时，并用（不用）ANG II（1 μmol/L）孵育 24 小时。
ANG II 增加（P<0.001）了心肌成纤维细胞中线粒体活性氧的产生，从 187.8±38.6 增加到 313.8±30.6 a.u./mg 线粒体蛋白（n=15）。ANG II 使 Prx-3 的 mRNA 和蛋白表达分别降低了 36.9±3.0%和 29.7±2.7%（n=4）。血管紧张素 1 型受体阻滞剂洛沙坦可阻止 ANG II 诱导的 Prx-3 mRNA 表达降低，但血管紧张素 2 型受体阻滞剂 PD 123319 则不能。
我们的数据表明，ANG II 刺激大鼠心肌成纤维细胞中线粒体活性氧的产生伴随着线粒体抗氧化剂 Prx-3 的表达减少，从而可能导致心肌的氧化应激。
