Péter Bencsik1,2, Viktor Sasi3, Krisztina Kiss1, Krisztina Kupai1, Márton Kolossváry4, Pál Maurovich-Horvat4, Tamás Csont5, Imre Ungi3, Béla Merkely4, Péter Ferdinandy2,6. 1. Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary. 2. Pharmahungary Group, Szeged, Hungary. 3. Division of Invasive Cardiology, Second Department of Internal Medicine and Center of Cardiology, University of Szeged, Szeged, Hungary. 4. MTA-SE Cardiovascular Imaging Research Group, Heart and Vascular Center, Semmelweis University, Budapest, Hungary. 5. Metabolic Diseases and Cell Signaling Research Group, Department of Biochemistry, University of Szeged, Budapest, Hungary. 6. Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
Abstract
AIMS: 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.
AIMS: 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 ureanitrogen (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 ureanitrogen with MMP-9 activity in patients with CAD. Studying the biomarkers of peroxynitrite-MMP pathway in large prospective trials may reveal their diagnostic avails.
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