title: Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase.
abstract: BACKGROUND
  There is growing recognition that oxidative stress plays a role in the pathogeneses of myocardial repair/remodeling following myocardial infarction (MI). Nicotinamide adenine denucleotide phosphate (NADPH) oxidase is a major source for cardiac reactive oxygen species production. Herein, we studied the importance of NADPH oxidase in development of cardiac oxidative stress and its induced molecular and cellular changes related to myocardial repair/remodeling.
  
  
  METHODS
  MI was created by coronary artery ligation in C57/BL (wild type) and NADPH oxidase (gp91(phox)) knockout mice. Cardiac oxidative stress, inflammatory/fibrogenic responses, apoptosis, and hypertrophy were detected by in situ hybridization, immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), picrosirius red staining, and image analysis, respectively, at different stages post MI.
  
  
  RESULTS
  In wild-type mice with MI, and compared to sham-operated animals, we observed significantly increased gp91(phox) and 3-nitrotyrosine, a marker of oxidative stress, in the infarcted myocardium; accumulated macrophages and myofibroblasts at the infarct site; abundant apoptotic myocytes primarily at border zones on Day 3; and numerous apoptotic inflammatory/myofibroblasts in the later stages. In addition, we detected significantly increased transforming growth factor beta1, tissue inhibitor of metalloprotease 2, and type 1 collagen gene expression; continuously increasing collagen volume in the infarcted myocardium; and hypertrophy in noninfarcted myocardium. Compared to wild-type mice with MI, we did not observe significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress in gp91(phox) knockout mice.
  
  
  CONCLUSIONS
  Our findings indicate that during NADPH oxidase deficiency, superoxide production can be compensated by other sources, which leads to cardiac oxidative stress and its related molecular/cellular events in the infarcted heart.
authors.affiliation: Department of Medicine, Division of Cardiovascular Diseases, University of Tennessee, Health Science Center, Memphis, TN 38163, USA.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.forename: Dawn
authors.initials: D
authors.lastname: Zhao
authors.forename: Ran
authors.initials: R
authors.lastname: Yan
authors.forename: Yao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D024042:Collagen Type I; D008562:Membrane Glycoproteins; D053773:Transforming Growth Factor beta1; D013481:Superoxides; D019716:Tissue Inhibitor of Metalloproteinase-2; C002744:3-nitrotyrosine; D014443:Tyrosine; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases