Cardioprotective Potential of ApoE-Derived Peptide (ApoEFrag) in Myocardial Infarction in Rats: A Mechanistic Study

Abstract

Cardiovascular diseases (CVDs) are the leading cause of death among non-communicable diseases globally. Myocardial infarction (MI) is one of the most significant CVDs resulting from acute or chronic myocardial ischemia, which can lead to irreversible damage. Despite the substantial burden posed by these conditions, specific treatments remain limited to symptomatic management. ApoEFrag has been shown to be protective in the CNS. However, the cardioprotective potential of ApoE-mimetic has not been investigated. Thus, this study investigates the cardioprotective potential of ApoEFrag, a novel ApoE-mimetic peptide, in an acute MI model in rats. MI was induced in rats through two doses of isoproterenol (100 mg/kg via subcutaneous injection) administered 24 h apart. ApoEFrag was given at doses of 0.5 and 1 mg/kg to ISO-treated rats. Following treatment, we measured electrocardiogram (ECG) changes and arterial and ventricular pressure functions using the PV-loop system. Plasma and heart samples were collected for biochemical assessments, including plasma injury markers, hypertrophic index parameters, inflammatory markers, gene/protein expression analysis, and histopathological studies. ISO-induced MI resulted in alterations in ECG patterns, ventricular dysfunction, increased fibrosis, and elevated hypertrophic index parameters. Additionally, ISO administration led to increased inflammatory markers and oxidative stress levels, which were reversed by the ApoEFrag treatment. Furthermore, ApoEFrag significantly ameliorated cardiac injury, inflammation, hypertrophic index parameters, ECG alterations, ventricular dysfunction, and cardiac fibrosis in ISO-induced MI models. Notably, ApoEFrag also improved mitochondrial health. This study suggests that ApoEFrag has significant cardioprotective potential in an acute myocardial infarction model.