Advanced glycation end products play a role in adverse LV remodeling following MI

Abstract

Purpose. There is a growing evidence that advanced glycation end products (AGEs) and their receptor (RAGE) play a key role in the development and progression of cardiovascular diseases. The study was therefore established to identify the role of RAGE expression on left ventricular (LV) function in a rat model of chronic myocardial infarction (MI).

Methods. 17 Sprague-Dawley rats were subjected to LAD ligation (MI; n=8) or sham surgery (SHAM; n=9). 2D echocardiography at baseline (BL) and 2 months post-surgery was used to calculate LV dimensions, volumes (EDV, ESV) and global functional parameters. Circulating plasma AGEs levels were determined by enzyme-linked immunosorbent assays (ELISA). Immunohistochemical staining and analysis of RAGE expression was performed in both groups at 2 months post-surgery.

Results. At 2 months post-MI, adverse cardiac failure was characterized by a significant increase in EDV and ESV respectively (0.2±0.04 to 0.8±0.2mL, and 0.04±0.02 to 0.5±0.1mL, p<0.05) along with depressed ejection fraction (EF) and fractional shortening (FS) compared to sham (32±11vs 76±9% and 14±7 vs 48±9%, p<0.05). Additionally, elevated plasma AGEs levels were observed along with significant upregulation in RAGE as compared to sham rats (23±6 vs 18±6 µg/ml and 0.28±0.06 vs 0.12±0.09, respectively). Increased tissue RAGE was associated with depressed EF and FS (R²=-0.66 and -0.73, respectively; fig.1).

Conclusion. Upregulation of RAGE is associated with decreased overall cardiac performance in the MI settings. Therapies targeting the AGEs-RAGE axis might be beneficial in the treatment of maladaptive remodeling following MI.