Abstract 53: PP1, a Derivative of Salubrinal, Ameliorate Ventricular Function After Myocardial Infarction in Rats
Objective: salubrinal, an inhibitor of ER-stress, has potent effect on cell injury. In this study, we investigated the effect of salubrinal and its derivative-PP1 on chronic heart failure induced by myocardial infarction ( MI).
Methods: Male wistar rats were randomly divided into 5 groups:i) sham-operated; ii) vehicle (MI+ DMSO); iii) MI + salubrinal; iv) MI + PP1; v) MI + kaptopril. After 6 weeks treatment, transthoracic echocardiographic and hemodynamic parameters were evaluated. The cardiac tissue sections were subjected to TUNEL to assess the level of apoptosis. The expression of mRNA and protein involved in apoptosis, autophagy, ER stress was analyzed using real-time reverse transcription-polymerase chain reaction and western blotting, respectively.
Results: The VW/BW and LVW/BW were reduced by salubrial and PP1.The LVEDD, LVESD were significantly decreased while the EF and FS were greatest increased by salubrinal and PP1. The hemodynamic parameters including CO, SV, LVEDV, LVESV, LVEDP, LVESP, +dp/dtmax, -dp/dtmax, +dv/dtmax, -dv/dtmax, Ea, Tau were ameliorated. By calculating the apoptotic index, we found that salubrinal and PP1 have a great anti-apoptotic effect. The mechanism analysis demonsted that salubrinal and PP1 have a cell protection effect through downregualtion of PERK, GRP78, chop, caspase12 and upregulation of p62 , LC3II, ATF4 as detected by real-time PCR and western blotting.
Conclusions: The current study suggested that salubrinal and PP1 have a cell protection effect involed in ER stress related autophay and apoptosis.This may implicate that salubrinal and PP1 may be a potent compound for the treatment of chronic heart failure.
Author Disclosures: C. Liu: None. Y. He: None. K. He: None.
- © 2015 by American Heart Association, Inc.