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Eur J Clin Invest. 2015 Jul;45(7):692-701. doi: 10.1111/eci.12458. Epub 2015 Jun 1.

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

Author information

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.

KEYWORDS:

Cardiac function; coronary artery disease; lipids; matrix metalloproteinase; nitro-oxidative stress; nitrotyrosine

PMID:
25944577
DOI:
10.1111/eci.12458
[Indexed for MEDLINE]

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