Serum Levels of Advanced Glycation End Products Are Associated with In-Stent Restenosis in Diabetic Patients

Abstract

The formation of advanced glycation end products (AGEs), in various tissues has been known to enhance immunoinflammatory reactions and local oxidant stresses in long standing diabetes. Recently, AGEs have been reported to play a role in neointimal formation in animal models of arterial injury. We attempted to determine whether the serum levels of AGEs are associated with coronary restenosis in diabetic patients. Blood samples were collected from diabetic patients with coronary artery disease undergoing stent implantation and the serum levels of AGEs were analyzed by the fluorescent intensity method. The development of in-stent restenosis (ISR) was evaluated by a 6-month follow-up coronary angiography. A total of 263 target lesions were evaluated, in 203 patients. The ISR rate in the high-AGE (>170 U/ml) group (40.1%) was significantly higher than in the low-AGE group (≤170 U/ml) (19.6%) (p<0.001). Furthermore, multivariate analysis revealed that a high level of serum AGEs is an independent risk factor for the development of ISR (odds ratio, 2.659; 95% CI, 1.431-4.940; p=0.002). The serum levels of AGEs constitute an excellent predictive factor for ISR, and should be one of the guidelines for medical therapy and interventional strategy to prevent ISR in diabetic patients.

Pathobiological role of advanced glycation endproducts via mitogen-activated protein kinase dependent pathway in the diabetic vasculopathy

“…Our previous serologic study of diabetic PCI patients revealed high serum levels of AGEs which was independent risk factor for ISR were significantly correlated with HbA 1 C and time duration of diabetes (Choi et al, 2005). Considering the in vitro and serologic study results, it can be explained that restenosis and increased atherosclerosis of the diabetic patients are related to the high serum levels of AGEs, which represented time dependent exposure of poor glycemic control.…”

“…Although, a few studies have identified the clinical and angiographic predictors of restenosis in diabetes patients, all the factors relating to the probability of restenosis after stent deployment in this high-risk patients subgroup are not known (West et al, 2004). Our previous study demonstrated that the rate of angiographic ISR was significantly higher in diabetic patients whose serum AGEs level was high compared with low AGEs group (Choi et al, 2005). In the current study we also demonstrated basal immunoreactivities of RAGE in human atheroma taken from diabetic patients.…”

Advanced glycation end product (AGE)-induced hepatic stellate cell activation via autophagy contributes to hepatitis C-related fibrosis

“…AGE levels are elevated in nonalcoholic steatohepatitis patients (NASH) [5] and chronic alcohol misuse patients [6,7]. There are no data on AGE levels in hepatitis C patients; however, AGE levels independently correlate with IR [8]. Our clinical data previously have shown that IR is closely associated with HCV infection and advanced liver cirrhosis [9].…”

Cariporide, a Specific Na⁺/H⁺ Exchanger 1 Blocker, Inhibits Neointimal Proliferation Induced by Advanced Glycation End Products in a Balloon Injury Rat Model

“…It has been demonstrated that wild-type mice undergoing arterial endothelial denudation displayed striking up-regulation of advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGE) in the injured vessel, particularly in activated smooth muscle cells of the expanding neointima [1,2,3]. AGEs can cause vascular damage through several mechanisms.…”