Low levels of soluble receptor for advanced glycation end products in non-ST elevation myocardial infarction patients
| Autor: | Jacobus Devilliers, Erick D. McNair, Rashpal S Basran, A. Mabood Qureshi, Calvin R. Wells, Jason Orvold, Kailash Prasad, Colin Pearce |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Acute coronary syndrome
medicine.medical_specialty Cell adhesion molecule business.industry medicine.medical_treatment medicine.disease RAGE (receptor) Proinflammatory cytokine Pathogenesis Endocrinology Cytokine Glycation Diabetes mellitus Internal medicine Immunology Medicine Original Article Cardiology and Cardiovascular Medicine business |
| Zdroj: | International Journal of Angiology. 18:187-192 |
| ISSN: | 1615-5939 1061-1711 |
| DOI: | 10.1055/s-0031-1278352 |
| Popis: | Advanced glycation end products (AGEs) are a heterogeneous group of irreversible adducts resulting from non-enzymatic glycation and oxidation of proteins, lipids and nucleic acids (1,2). AGEs act on cell receptors for AGEs (RAGEs). There are three forms of RAGEs (2–5) – full-length, N-truncated and C-truncated soluble RAGEs (sRAGE). The interaction of full-length RAGE with AGEs leads to increased expression of adhesion molecules, including soluble vascular cell adhesion molecule-1 (sVCAM-1) and the cytokine tumor necrosis factor-alpha (TNF-α) (2,6,7); activation of nuclear factor-kappa B (6), which in turn leads to increased expression of proinflammatory genes for adhesion molecules and cytokines (2); and generation of oxygen radicals (8,9). sRAGE circulates in the plasma (4) and acts as a decoy for RAGE ligands, competing with full-length RAGE for ligand binding (10). It has a protective role by preventing the activation of full-length RAGE. Adhesion molecules, cytokines and oxygen radicals are involved in atherosclerosis, progression of lesions and lesion instability (11–14). The AGEs and RAGE axis has been implicated in the pathogenesis of atherosclerosis in diabetes (15–17). sRAGE in animal models reduces atherosclerotic lesions, aortic vascular cell adhesion molecule-1 and tissue factor (18–20). The proximate cause of acute coronary syndrome (ACS) is thrombosis and the principal underlying cause is atherosclerosis. Because the combination of AGEs, RAGEs and sRAGE determines the extent of vascular injury, the measurement of these factors is appropriate for determining vascular complications. However, it is not possible to measure RAGE in humans, which is on the cell surface of the artery. It is hypothesized that non-ST elevation myocardial infarction (NSTEMI) patients have lower levels of serum sRAGE and/or higher levels of AGEs, and a higher ratio of AGEs to sRAGE (AGEs/sRAGE) than healthy subjects. Because the interaction of RAGE with AGEs results in increased expression of cytokines and adhesion molecules, and because sRAGE neutralizes AGEs, low sRAGE levels would be associated with high levels of TNF-α and sVCAM-1. Therefore, the main objectives of the present study are to determine whether levels of serum sRAGE are lower, and whether levels of serum AGEs and AGEs/sRAGE are higher in NSTEMI patients than in healthy subjects; whether low levels of serum sRAGE, and high levels of serum AGEs and AGEs/sRAGE are associated with high levels of serum TNF-α and sVCAM-1; whether the number of diseased coronary arteries is negatively correlated with serum sRAGE and positively correlated with serum TNF-α, sVCAM-1, AGEs and AGEs/sRAGE; and whether the level of sRAGE or AGEs/sRAGE is a better biomarker/predictor of NSTEMI. |
| Databáze: | OpenAIRE |
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