Post-myocardial infarction heart failure and long-term high-fat diet: Cardiac endoplasmic reticulum stress and unfolded protein response in Sprague Dawley rat model

PLoS One. 2024 Sep 18;19(9):e0308833. doi: 10.1371/journal.pone.0308833. eCollection 2024.

Abstract

Background: Myocardial infarction (MI) significantly contributes to the global mortality rate, often leading to heart failure (HF) due to left ventricular remodeling. Key factors in the pathomechanism of HF include nitrosative/oxidative stress, inflammation, and endoplasmic reticulum (ER) stress. Furthermore, while a high-fat diet (HFD) is known to exacerbate post-MI cardiac remodeling, its impact on these critical factors in the context of HF is not as well understood.

Aims: This study aimed to assess the impact of post-MI HF and HFD on inflammation, nitro-oxidative stress, ER stress, and unfolded protein response (UPR).

Methods: The study was performed on fragments of the left ventricle harvested from 30 male adult Sprague Dawley rats, which were divided into four groups based on diet (normal-fat vs. high-fat) and surgical procedure (sham operation vs. coronary artery ligation to induce MI). We assessed body weight, NT-proBNP levels, protein levels related to nitrosative/oxidative stress, ER stress, UPR, apoptosis, and nitric oxide synthases, through Western Blot and ELISA.

Results: HFD and MI significantly influenced body weight and NT-proBNP concentrations. HFD elevated 3-nitrotyrosine and myeloperoxidase levels and altered nitric oxide synthase levels. HFD and MI significantly affected ER stress markers and activated or inhibited UPR pathways.

Conclusions: The study demonstrates significant impacts of post-MI HF and dietary fat content on cardiac function and stress markers in a rat model. The interaction between HFD and MI on UPR activation suggests the importance of dietary management in post-MI recovery and HF prevention.

MeSH terms

  • Animals
  • Apoptosis
  • Diet, High-Fat* / adverse effects
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress*
  • Heart Failure* / etiology
  • Heart Failure* / metabolism
  • Heart Failure* / pathology
  • Male
  • Myocardial Infarction* / metabolism
  • Myocardial Infarction* / pathology
  • Myocardium / metabolism
  • Myocardium / pathology
  • Natriuretic Peptide, Brain / metabolism
  • Oxidative Stress*
  • Peptide Fragments / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Unfolded Protein Response*

Substances

  • Natriuretic Peptide, Brain
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)

Grants and funding

This study was financed by a research grant from the Medical University of Warsaw (1MA/2/M/MG/N/23) to [KK] https://pnitt.wum.edu.pl/en The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.