title: Differential expression of Nad(P)H oxidase isoforms and the effects of atorvastatin on cardiac remodeling in two-kidney two-clip hypertensive rats.
abstract: 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.
authors.affiliation: Laboratory of Pharmacology and Molecular Biology, Medical College, Henan University of Science and Technology, Luoyang, Henan Province, China. liruifang1234@yahoo.com.cn
authors.forename: Ruifang
authors.initials: R
authors.lastname: Li
authors.forename: Weijin
authors.initials: W
authors.lastname: Fang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jiangang
authors.initials: J
authors.lastname: Wang
authors.forename: Shoumin
authors.initials: S
authors.lastname: Xi
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yunxia
authors.initials: Y
authors.lastname: He
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis; D015153:Blotting, Western; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006978:Hypertension, Renovascular / Q000150:complications* / Q000473:pathology; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018487:Ventricular Dysfunction, Left / Q000473:pathology / Q000517:prevention & control; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; C000594638:MYH7 protein, rat; D008562:Membrane Glycoproteins; D011758:Pyrroles; D017382:Reactive Oxygen Species; D009320:Atrial Natriuretic Factor; D000069059:Atorvastatin; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C060505:neutrophil cytosolic factor 1; D018995:Myosin Heavy Chains