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DOI: 10.1055/s-0039-1678968
AGE and RAGE in the Aortic Aneurysm of Patients with Bicuspid Aortic Valve
Publikationsverlauf
Publikationsdatum:
28. Januar 2019 (online)
Objectives: Advanced glycation end products (AGEs) are known to form cross-linkages within the extracellular matrix and between the collagen fibrils leading to progressive arterial stiffness. Investigation of the soluble fraction of the receptor of AGEs (RAGE) in serum samples of patients with bicuspid aortic valve (BAV) and associated aortopathy have shown a significant increase compared to patients with a tricuspid aortic valve (TAV) discussing the potential of RAGE as a biomarker. The aim of the study was to evaluate AGE and RAGE in the aortic tissue of patients with BAV receiving tubular/ascending aortic replacement.
Methods: Aortic specimen of 93 patients (51 BAV, 42 TAV) - distinguishing convex and concave side - and blood samples were investigated concerning AGE and RAGE utilizing western blot and ELISA technique. Localization within the aortic wall was visualized via histochemistry. Patients with diabetes were excluded due to known accumulation of AGEs in those patients.
Results: Patients with BAV were significantly younger at time of surgery (56 ± 15 vs. 65 ± 11, p = 0.005) compared to patients with a TAV. Aortic aneurysm diameter was not significantly different (BAV: 49.1 ± 4.7 vs. TAV: 50.4 ± 8.7, p = 0.393). In the western blot analysis, the expression of AGE (convex: BAV: 1.57 ± 0.93 vs. TAV: 1.03 ± 0061; p = 0.011, concave: BAV: 1.63 ± 0.88 vs. TAV: 0.97 ± 0.76; p = 0.003) and RAGE (convex: BAV: 1.91 ± 1.57 vs. TAV: 0.94 ± 0.44; p < 0.001, concave: BAV: 1.94 ± 1.26 versus TAV: 0.79 ± 0.52; p < 0.001) was significantly higher in BAV patients, showing no significant difference between convex and concave site within each group. Results were confirmed by ELISA. Histology showed homogenous distribution of AGE across all three layers of the aortic wall with higher intensity in BAV patients. However, no relevant difference in plasma levels of AGE (BAV: 6.89 ± 4.40 vs. TAV: 6.43 ± 4.11, p = 0.718) and RAGE (BAV: 58.70 ± 44.04 vs. TAV: 41.30 ± 37.46, p = 0.169) was observed.
Conclusions: Patients with a BAV experience a higher level of AGE and their receptor RAGE within the aortic wall potentially leading to an increase in aortic stiffness further elevating the cardiovascular risk. However, plasma samples of the same patients did not reflect this increase within the aortic wall questioning AGE and RAGE as potential biomarkers.