Glycation and cardiovascular disease in diabetes: A perspective on the concept of metabolic memory

Abstract

Epidemiological studies have suggested that cumulative diabetic exposure, namely prolonged exposure to chronic hyperglycemia, contributes to the increased risk of cardiovascular disease (CVD) in diabetes. The formation and accumulation of advanced glycation end-products (AGEs) have been known to progress under hyperglycemic conditions. Because AGEs-modified collagens are hardly degraded and remain in diabetic vessels, kidneys and the heart for a long time, even after glycemic control has been achieved, AGEs could become a marker reflecting cumulative diabetic exposure. Furthermore, there is a growing body of evidence that an interaction between AGEs and the receptor for AGEs (RAGE) plays a role in the pathogenesis of CVD. In addition, AGEs induce the expression of RAGE, thus leading to sustained activation of the AGEs-RAGE axis in diabetes. Herein we review the pathological role of the AGEs-RAGE axis in CVD, focusing particularly on the phenomenon of metabolic memory, and discuss the potential clinical usefulness of measuring circulating and tissue levels of AGEs accumulation to evaluate diabetic macrovascular complications.

Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling

“…In diabetic myocardium, mitochondria is deemed as one of the major sources of free radicals. Numerous studies have reported that hyperglycemia markedly impaired mitochondrial morphology and function, causing electron leakage and O 2 •− generation2526. The enhanced oxidative stress has been confirmed to be a key contributor to increased myocardial vulnerablility to MI/R injury25.…”

“…To make things worse, the long-term prognosis is also much worse than non-diabetic individuals with higher rates of residual ventricular dysfunction and overall mortality2324. So far, the mechanisms have not been fully elucidated, but prolonged hyperglycemia-enhanced oxidative stress was indicated to be a crucial contributor25. Owing to its critical role in generating ATP and ROS, cardiomyocyte mitochondria has been specifically investigated.…”

Combined Effects of Curcumin and Lycopene or Bixin in Yoghurt on Inhibition of LDL Oxidation and Increases in HDL and Paraoxonase Levels in Streptozotocin-Diabetic Rats

“…Oxidative stress is one mechanism that participates in the establishment of microvascular [69] and macrovascular [70] complications even after maintenance of normoglycemia under intensive antihyperglycemic treatment, a phenomenon often referred to as “metabolic memory.” In front of this, complementary therapies targeting not only the hyperglycemia but also other metabolic disturbances in diabetes mellitus (DM), such as oxidative stress, are appearing as promising strategies in combating diabetic complications [71]. …”

Role of Advanced Glycation Endproduct (AGE)-Receptor for Advanced Glycation Endproduct (RAGE) Axis in Cardiovascular Disease and Its Therapeutic Intervention

“…[6][7][8][9][10][11][12][13][14][15][16] There is accumulating evidence to show the pathophysiological involvement of "metabolic memory" in vascular complications in diabetes. 17 Indeed, although intensive management of blood glucose for 6.5-10 years did not significantly reduce the risk of CVD or death in both type 1 and 2 diabetic patients, the 10-30-year follow-up studies sured as skin autofluorescence (SAF) by an AGE-Reader (Diagnoptics, Groningen, Netherlands). 24,25 SAF is defined as the ratio of average autofluorescence over the entire 420-600-nm emission spectrum to that over 300-420 nm, which correlates with pentosidine and N ε -(carboxymethyl) lysine (CML), well-characterized fluorescent and nonfluorescent AGEs, respectively, in the skin.…”