Accumulation of advanced glycation end products (AGEs) is associated with the severity of aortic stenosis in patients with concomitant type 2 diabetes

Abstract

Abstract Background Accumulation of advanced glycation end products (AGEs) leads to chronic glycation of proteins and tissue damage, particularly in patients with diabetes mellitus (DM). We aimed to evaluate whether increased accumulation of AGEs in patients with aortic stenosis (AS) and concomitant type 2 diabetes (DM) is associated with AS severity. Methods We prospectively enrolled 76 patients with severe AS (47.1% males; nonDM), aged 68 [66–72] years, and 50 age-matched DM patients with a median blood glucose level of 7.5 [5.9–9.1] mM and glycated hemoglobin (HbA1c) of 6.8 [6.3–7.8]%, scheduled for aortic valve replacement. Valvular expression of AGEs, AGEs receptor (RAGE), interleukin-6 (IL-6), and reactive oxygen species (ROS) induction were evaluated ex vivo by immunostaining and calculated as the extent of positive immunoreactive areas/total sample area. Plasma levels of AGEs and soluble RAGE (sRAGE) were assessed by ELISAs. Results Subjects with DM had increased valvular expression of both AGEs (6.6-fold higher, 15.53 [9.96–23.28]%) and RAGE (1.8-fold higher, 6.8 [4.9–8.45]%) compared to nonDM patients (2.05 [1.21–2.58]% and 2.4 [1.56–3.02]%, respectively; both p 7% (n = 24, 48%) we found that valvular expression of AGEs correlated with mean transvalvular pressure gradient (PGmean; r = 0.45, p = 0.027). Plasma AGEs levels in the whole DM group correlated with AVA (r = − 0.32, p = 0.02), PGmean (r = 0.31, p = 0.023), and PGmax (r = 0.30, p = 0.03). Conclusions Our study suggests that poorly-controlled diabetes leads to increased AGEs and RAGE valvular accumulation, which at least partially, might result in AS progression in DM patients.

Keywords

• Aortic stenosis (AS)
• Diabetes mellitus (DM)
• Advanced glycation end products (AGEs)
• Inflammation
• Oxidative stress