A sirtuin 1/MMP2 prognostic index for myocardial infarction in patients with advanced coronary artery disease

• Published in: International journal of cardiology Vol. 230; pp. 447 - 453
• Main Authors: Doulamis, Ilias P., Tzani, Aspasia I., Konstantopoulos, Panagiotis S., Samanidis, George, Georgiopoulos, Georgios, Toutouzas, Konstantinos P., Perrea, Despina N., Perreas, Konstantinos G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2017
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers - blood; Cardiac remodeling; Cardiovascular; Coronary Artery Bypass; Coronary artery disease; Coronary Artery Disease - blood; Coronary Artery Disease - complications; Coronary Artery Disease - surgery; Endothelial dysfunction; Female; Humans; Male; Matrix Metalloproteinase 2 - blood; Middle Aged; Myocardial infarction; Myocardial Infarction - blood; Myocardial Infarction - diagnosis; Myocardial Infarction - etiology; Predictive Value of Tests; Prognosis; Prognostic index; Prospective Studies; Sirtuin 1 - blood; Myocardial infarction; Endothelial dysfunction; Cardiac remodeling; Prognostic index; Coronary artery disease
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2016.12.086

Sirtuin 1 (SIRT1) appears to play a protective role against endothelial dysfunction and oxidative stress. Instead, matrix metalloproteinase 2 (MMP2) is involved in acute coronary events, by promoting tissue remodeling. This study sought to determine the clinical value of a prognostic index arising from the combination of these two biomarkers for myocardial infarction (MI) in patients with advanced coronary artery disease. Eighty-one patients with advanced coronary artery disease planned for open heart surgery were prospectively enrolled. Serum levels of SIRT1 and MMP2 were measured by ELISA. To look at the relation of these mediators with clinical characteristics, pre-operative data and patients demographics were collected. SIRT1 levels correlated marginally with a history of hypertension (ρ=0.2, p=0.084) and inversely with baseline urea (ρ=0.25, p=0.056). When performing additional adjustment, low SIRT1 levels were independently associated with diabetes mellitus 2(DM2) and subjects with SIRT1 <2.95ng/mL were more prone to present DM2 (82% sensitivity and 62% specificity). The index of low SIRT1 and high MMP2 respectively correlated with patients history of MI (ρ=0.3, p=0.01) and marginally with presence or history of atrial fibrillation (AF) (ρ=0.213, p=0.076). When adjusting for anthropometric and comorbidities, the combined index tended to have an association with impaired ejection fraction (EF)<55% (p=0.059). The combined index of low SIRT1 and high MMP2 exhibited a significant correlation with history of MI and EF, promoting a potential prognostic tool for MI incidence in patients regardless their coronary artery disease status. SIRT1 mainly depicts the cardiac functionality on a vascular level, whilst MMP2 demonstrates it via the aspect of heart contractility. Thus, a combined index of SIRT1 and MMP2 provides us with a global overview of the risk for MI. Specifically, low SIRT1 levels in addition to high levels of MMP2 favor the incidence of MI. *SIRT1: sirtuin 1; MMP2: matrix metalloproteinase 2; AROS: Active regulator of SIRT1; IL-21: interleukin 21; mTOR: mammalian target of rapamycin; NF-kB: nuclear factor kappa-light-chain-enhancer of activated B cells; eNOS: endothelial nitric oxide synthase; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator 1-alpha; FOXO 3: Forkhead box O3; ECM: extracellular matrix; VEGF: vascular endothelial growth factor; TNF-α: tumor necrosis factor alpha; CVD: cardiovascular disease; MI: myocardial infarction; LVEF: left ventricular ejection fraction. [Display omitted]