title: Neutrophils recruited to the myocardium after acute experimental myocardial infarct generate hypochlorous acid that oxidizes cardiac myoglobin.
abstract: Myocardial inflammation following acute myocardial infarct (AMI) is associated with risk of congestive heart failure. Pro-inflammatory neutrophils were recruited to the damaged myocardium 24 h after permanent coronary ligation in rats to induce AMI as judged by the presence of immune-positive myeloperoxidase (MPO) in the tissues; MPO generates the oxidant hypochlorous acid (HOCl). Neutrophils were absent in hearts from Control (untreated) and surgical Sham. Similarly, rats exposed to 1 h coronary ligation (Ischemia) showed no neutrophil infiltrate. Concomitantly, MPO activity increased in left ventricular (LV) homogenates prepared from the AMI group and this was inhibited by paracetamol and the nitroxide TEMPO. The same LV-homogenates showed increased 3-chlorotyrosine/tyrosine ratios (biomarker for MPO-activity). Combined 2D gel/Western blot indicated cardiac myoglobin (Mb) was modified after AMI. Subsequent MALDI-TOF and LC-MS/MS analysis of isolated protein spots revealed increased Mb oxidation in hearts from the AMI group relative to Control, Sham and Ischemia groups. Peptide mass mapping revealed oxidation of Met9 and Met132 to the corresponding sulfoxides yet Cys67 remained unmodified. Therefore, neutrophil-generated HOCl can oxidize cardiac Mb after AMI and this may impact on its function within the affected myocardium: oxidized Mb maybe a useful marker of myocardial inflammation.
authors: Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, The University of Sydney, Australia.
authors: Xiao Suo
authors: XS
authors: Wang
authors: Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, The University of Sydney, Australia.
authors: Hyun Bo
authors: HB
authors: Kim
authors: ANZAC Research Institute, Concord Hospital, NSW, 2139, Australia.
authors: Andrea
authors: A
authors: Szuchman-Sapir
authors: ANZAC Research Institute, Concord Hospital, NSW, 2139, Australia.
authors: Aisling
authors: A
authors: McMahon
authors: Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, The University of Sydney, Australia.
authors: Joanne M
authors: JM
authors: Dennis
authors: Discipline of Pathology, Sydney Medical School, The University of Sydney, NSW, 2006, Australia; Charles Perkins Centre, The University of Sydney, Australia. Electronic address: paul.witting@sydney.edu.au.
authors: Paul K
authors: PK
authors: Witting
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D006997:Hypochlorous Acid / Q000737:chemistry*; D007150:Immunohistochemistry; D007249:Inflammation; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009211:Myoglobin / Q000737:chemistry*; D009504:Neutrophils / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013454:Sulfoxides / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D009211:Myoglobin; D013454:Sulfoxides; D006997:Hypochlorous Acid; D010100:Oxygen
keywords: Heart attack; Hypochlorous acid; Mass spectrometry; Myoglobin; Neutrophil; Peptide mass mapping