Journal of diabetes research
The AGEs/RAGE Axis Contributes to Myocardial Cell Death in Type 1 Diabetic Cardiomyopathy via the ROS/NF-κB/NLRP3 Inflammasome Pathway
By Li X, Chen S, Wang K and 4 others.
Abstract
Background
Type 1 diabetes mellitus (T1DM) cardiomyopathy is a severe complication that typically follows an insidious onset and then progresses rapidly to heart failure and premature death. AGEs accumulate in the myocardium under hyperglycemic conditions and have emerged as important mediators of this diabetic complication, although the full signaling cascades engaged by AGEs remain largely unresolved. In the present study, we therefore investigated whether AGEs induce myocardial injury in T1DM via NLRP3 inflammasome activation.
Methods
A T1DM mouse model was established using streptozotocin (STZ) injections, and an in vitro model was generated by treating primary neonatal mouse cardiomyocytes with AGEs. Cardiac performance and morphological changes were examined via echocardiography and histopathological staining. Expression and activation of the NLRP3 signaling cascade were evaluated by Western blotting, ELISA, and immunofluorescence. Pyroptotic cell death was assessed by SYTOX green staining, PI uptake, and lactate dehydrogenase (LDH) release assay. Correlations between whole-blood RAGE gene expression and inflammatory cytokine levels (IL-1β and IL-18) in T1DM patients, along with myocardial abundance of RAGE, NLRP3, and N-GSDMD in the experimental mice, were analyzed as exploratory descriptive observations.