Efficacy of Semaglutide in Modulating Cardiac Remodeling in  Mice: A Review of Mechanisms and Outcomes

Reenal  Fairy; Laiba  Ali; Hafsa  Azam; Aaminah  Khurram; Mohammad  Shahzaib; Hafsa  Tariq; Syeda  Rashmeen; Haris  Hassan

doi:10.18502/jthc.v20i3.20114

Reenal Fairy Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Laiba Ali Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Hafsa Azam Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Aaminah Khurram Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Mohammad Shahzaib Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Hafsa Tariq Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Syeda Rashmeen Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.
Haris Hassan Department of Medicine, Jinnah Sindh Medical University, Karachi, Pakistan.

DOI: https://doi.org/10.18502/jthc.v20i3.20114

Keywords: Cardiac Remodeling; Cardiac Hypertrophy; Cardioprotection; Heart Failure; Oxidative Stress; Inflammation; Apoptosis; Semaglutide; Glucagon-Like Peptide

Abstract

Objective: This review evaluates the efficacy of semaglutide in reducing cardiac hypertrophy and enhancing cardiac function in mouse studies.

Methods: A literature search was conducted using databases such as PubMed, Google Scholar, SpringerLink, Cochrane, Nature, JACC, and ScienceDirect. Keywords included “semaglutide,” “cardiac remodeling,” “heart failure,” “heart failure with preserved ejection fraction (HFpEF),” and “cardiac hypertrophy.” Studies involving male and female mice that discussed the effects of semaglutide on hypertrophy, oxidative stress, inflammatory markers, and cardiac remodeling were included. Data were extracted using the PICO framework.

Results: Semaglutide consistently led to reductions in body weight, fat mass, tissue-specific inflammation, apoptosis, and oxidative stress in mice. It significantly alleviated cardiac hypertrophy, as evidenced by decreased heart weight and left ventricular mass, and improved cardiac output through enhanced cellular architecture. Inflammatory markers such as tumor necrosis factor α, interleukin 6, and atrial natriuretic peptide were notably reduced. Fibrosis was significantly attenuated at both molecular and histological levels, with decreased collagen deposition and lower markers such as collagen 1a1 and collagen 3a1. Oxidative stress markers NADPH oxidase 2 and malondialdehyde were reduced, accompanied by increased antioxidant enzymes, including superoxide dismutase and catalase. Additionally, semaglutide reduced apoptosis, evidenced by lower levels of Bcl-2-associated X protein (BAX) and slightly decreased caspase-3.

Conclusion: The results demonstrate the significant potential of semaglutide for managing cardiac remodeling. Semaglutide showed considerable cardioprotective effects through the regulation of hypertrophy, oxidative stress, inflammation, apoptosis, fibrosis, and lipid metabolism. These benefits suggest its viability as a promising therapeutic agent for cardiac disorders. Nonetheless, more clinical trials, particularly in humans, are required to validate these findings and determine appropriate dosing.