title: Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in coronary artery disease patients.
abstract: OBJECTIVE
  Peroxynitrite-matrix metalloproteinase (MMP) signalling has been shown to contribute to myocardial ischaemia/reperfusion injury and heart failure and to be influenced by hyperlipidaemia in preclinical models. Therefore, here we investigated the correlation between the markers of peroxynitrite-MMP signalling and hyperlipidaemia in patients with significant coronary stenosis.
  
  
  METHODS
  Five minutes before percutaneous coronary intervention (PCI), arterial blood samples were collected from 36 consecutive patients with coronary artery disease (CAD) selected for elective PCI.
  
  
  RESULTS
  Serum nitrotyrosine positively correlated with MMP-9 activity (r = 0·54, P = 0·01), but not with MMP-2 activity. Nitrotyrosine positively correlated with total (r = 0·58; P < 0·01) and LDL cholesterol (r = 0·55; P < 0·01), serum triglyceride (r = 0·47; P < 0·05), and creatinine (r = 0·42; P < 0·05) and negatively correlated with HDL cholesterol (r = -0·46; P < 0·05) and with left ventricular ejection fraction (LVEF; r = -0·55; P < 0·05), respectively. MMP-2 activity correlated positively with total (r = 0·55; P < 0·05) and LDL cholesterol (r = 0·45; P < 0·05). In statin-treated patients, a significantly reduced serum nitrotyrosine was found as compared to statin naives; however, MMP activities and serum cholesterol levels were not different. MMP-9 activity correlated with urea nitrogen (r = 0·42; P < 0·05) and LVEF (r = -0·73; P < 0·01). Serum creatinine correlated negatively with LVEF (r = -0·50, P < 0·01).
  
  
  CONCLUSIONS
  This is the first demonstration that (i) serum nitrotyrosine correlates with MMP-9 activity, (ii) lipid parameters correlate with nitrotyrosine and MMP-2 activity, (iii) myocardial function correlates with creatinine, nitrotyrosine and MMP-9 activity, and (iv) creatinine correlates with nitrotyrosine and urea nitrogen with MMP-9 activity in patients with CAD. Studying the biomarkers of peroxynitrite-MMP pathway in large prospective trials may reveal their diagnostic avails.
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.|Pharmahungary Group, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Bencsik
authors.affiliation: Division of Invasive Cardiology, Second Department of Internal Medicine and Center of Cardiology, University of Szeged, Szeged, Hungary.
authors.forename: Viktor
authors.initials: V
authors.lastname: Sasi
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kiss
authors.affiliation: Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Kupai
authors.affiliation: MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Kolossváry
authors.affiliation: MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Pál
authors.initials: P
authors.lastname: Maurovich-Horvat
authors.affiliation: Metabolic Diseases and Cell Signaling Research Group, Department of Biochemistry, University of Szeged, Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.affiliation: Division of Invasive Cardiology, Second Department of Internal Medicine and Center of Cardiology, University of Szeged, Szeged, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Ungi
authors.affiliation: MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Pharmahungary Group, Szeged, Hungary.|Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000097:blood* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000502:physiology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010865:Pilot Projects; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014508:Urea / Q000737:chemistry
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C002744:3-nitrotyrosine; D014443:Tyrosine; D014508:Urea; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D009584:Nitrogen
keywords: Cardiac function; coronary artery disease; lipids; matrix metalloproteinase; nitro-oxidative stress; nitrotyrosine