Serum lipids and cardiac function correlate with nitrotyrosine and MMP activity in coronary artery disease patients

Abstract

AIMS: Peroxynitrite - matrix metalloproteinase (MMP) signaling has been shown to contribute to myocardial ischemia/reperfusion injury and heart failure and to be influenced by hyperlipidemia in preclinical models. Therefore, here we investigated the correlation between the markers of peroxynitrite - MMP signaling and hyperlipidemia in patients with significant coronary stenosis. METHODS: Five minutes before percutaneous coronary intervention (PCI), arterial blood samples were collected from 36 consecutive coronary artery disease (CAD) patients 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=-0.49, p<0.05). 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 CAD patients. Studying the biomarkers of peroxynitrite - MMP pathway in large prospective trials may reveal their diagnostic avails. This article is protected by copyright. All rights reserved.