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.