Li Ruifang, Fang Weijin, Cao Shanshan, Li Yan, Wang Jiangang, Xi Shoumin, Zhang Bo, He Yunxia
Laboratory of Pharmacology and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China.
Pharmazie. 2013 Apr;68(4):261-9.
The NADPH oxidases (Noxes) are a family of ROS (reactive oxygen species)-generating enzymes which play a critical role in the development of cardiac remodeling associated with heart failure. The Noxes of their catalytic isoforms include multiple homologues in cardiovascular cells with wide range tissue distribution. It is still unclear which Noxes represent the major enzymatic source of ROS in the heart and play a predominant role in cardiac hypertrophy. In this study we investigated the differential expression changes of NAD(P)H oxidase P47phox isoform and Nox homologues in left ventricle and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip(2K2C) hypertensive rats. The mRNA and protein expression of Nox2, Nox4 and P47phox showed a sustained increase at 4, 8, 12 weeks after surgery in 2K2C rats. Administration of atorvastatin attenuated cardiac dysfunction, hypertrophy and fibrosis of 2K2C rats. However, atorvastatin treatment had no effects on BP regulation. Further studies revealed that atorvastatin inhibited the increased expression of Nox2, Nox4, P47phox as well as 02"- production in 2K2C hypertensive rats. These findings indicate that Nox2, Nox4 and P47phox play a crucial role in the development of cardiac remodeling in the 2K2C hypertensive rats. Atorvastatin, independent of BP control, exerts anti-remodeling effects partially by inhibition of NAD(P)H oxidase-mediated cardiac oxidative stress.
NADPH氧化酶（Noxes）是一类产生活性氧（ROS）的酶家族，在与心力衰竭相关的心脏重塑发展过程中起关键作用。其催化同工型的Noxes在心血管细胞中有多个同源物，组织分布广泛。目前仍不清楚哪种Noxes是心脏中ROS的主要酶来源，并在心肌肥大中起主要作用。在本研究中，我们调查了两肾双夹（2K2C）高血压大鼠左心室中NAD（P）H氧化酶P47phox同工型和Nox同源物的差异表达变化，以及阿托伐他汀对心脏重塑的影响。Nox2、Nox4和P47phox的mRNA和蛋白表达在2K2C大鼠术后4周、8周、12周持续增加。给予阿托伐他汀可减轻2K2C大鼠的心脏功能障碍、肥大和纤维化。然而，阿托伐他汀治疗对血压调节无影响。进一步研究表明，阿托伐他汀可抑制2K2C高血压大鼠中Nox2、Nox4、P47phox的表达增加以及超氧阴离子的产生。这些发现表明，Nox2、Nox4和P47phox在2K2C高血压大鼠心脏重塑的发展中起关键作用。阿托伐他汀独立于血压控制，部分通过抑制NAD（P）H氧化酶介导的心脏氧化应激发挥抗重塑作用。
