Inverse Association between Cardiac Troponin-I and Soluble Receptor for Advanced Glycation End Products in Patients with Non-ST-Segment Elevation Myocardial Infarction

Abstract

Interaction of advanced glycation end products (AGEs) with the receptor for advanced AGEs (RAGE) results in activation of nuclear factor kappa-B, release of cytokines, expression of adhesion molecules, and induction of oxidative stress. Oxygen radicals are involved in plaque rupture contributing to thromboembolism, resulting in acute coronary syndrome (ACS). Thromboembolism and the direct effect of oxygen radicals on myocardial cells cause cardiac damage that results in the release of cardiac troponin-I (cTnI) and other biochemical markers. The soluble RAGE (sRAGE) compete with RAGE for binding with AGE, thus functioning as a decoy and exerting a cytoprotective effect. Low levels of serum sRAGE would allow unopposed serum AGE availability for binding with RAGE, resulting in the generation of oxygen radicals and proinflammatory molecules that have deleterious consequences and promote myocardial damage. sRAGE may stabilize atherosclerotic plaques. It is hypothesized that low levels of sRAGE are associated with high levels of serum cTnI in patients with ACS. The main objective of the study was to determine whether low levels of serum sRAGE are associated with high levels of serum cTnI in ACS patients. The serum levels of sRAGE and cTnI were measured in 36 patients with non-STsegment elevation myocardial infarction (NSTEMI) and 30 control subjects. Serum levels of sRAGE were lower in NSTEMI patients (802.56 AE 39.32 pg/mL) as compared with control subjects (1311.43 AE 66.92 pg/mL). The levels of cTnI were higher in NSTEMI patients (2.18 AE 0.33 mg/mL) as compared with control subjects (0.012 AE 0.001 mg/mL). Serum sRAGE levels were negatively correlated with the levels of cTnI. In conclusion, the data suggest that low levels of serum sRAGE are associated with high serum levels of cTnI and that there is a negative correlation between sRAGE and cTnI.

Soluble Receptor for Glycation End-products Concentration Increases Following the Treatment of Severe Diabetic Ketoacidosis

“…However, low sRAGE concentrations are reported to occur in various conditions during the acute clinical phase in addition to changes reported in DKA. These conditions include: 1) atrial fibrillation (33); 2) low sRAGE and high cardiac troponin in non-ST segment elevation myocardial infarction (34); and 3) the autoimmune condition of multiple sclerosis (35).…”

The Relationship between Plasma Soluble Receptor for Advanced Glycation End Products and Coronary Artery Disease

“…However, patients with non-ST elevation myocardial infarction did not have elevated sRAGE due to the weaker inflammatory response. McNair et al [11, 22] found that plasma sRAGE levels were decreased in patients with non-ST-segment elevation myocardial infarction, while the levels of TNF- α and hypersensitive C-reactive protein increased. Whether in the control group or the infarction group, the level of sRAGE was negatively correlated with TNF- α and high-sensitivity C-reactive protein.…”

“…RAGE, a multiligand receptor, interacts with a variety of ligands including the AGEs, S100 calcium-binding protein family, high-mobility group box 1 (HMGB1), beta amyloid-like peptides, and β 2 integrins [2, 5, 7]. The binding of RAGE with its ligands results in amplifying the inflammatory response and tissue injury via the activation of nuclear factor kappa-B, the release of cytokines, the expression of adhesion molecules, and the generation of reactive oxygen species, contributing to the pathogenesis of atherosclerosis and plaque rupture [8–11].…”

“…However, Basta et al [18] found that sRAGE levels did not differ between the NSTE-ACS group and the stable angina group. McNair et al [11] showed that serum sRAGE levels were lower in NSTEMI patients than in healthy control subjects and inversely related to the number of diseased vessels.…”

Soluble Receptor for Advanced Glycation End Product: A Biomarker for Acute Coronary Syndrome

“…Blood samples were collected before the revascularization. Similarly, McNair et al found lower levels of sRAGE in patients with non-STEMI compared to the controls, and time of blood sample collection was not indicated [ 51 – 54 ].…”