Ghrelin ameliorates cardiac fibrosis after myocardial infarction by regulating the Nrf2/NADPH/ROS pathway

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Fibrosis Research

Background:

• Cardiac fibrosis is a significant complication following myocardial infarction (MI).
• The role of ghrelin and its downstream signaling in mitigating cardiac fibrosis remains incompletely understood.
• Oxidative stress pathways, including NADPH oxidase and reactive oxygen species (ROS), are implicated in cardiac remodeling and fibrosis.

Purpose of the Study:

• To investigate the cardioprotective role of ghrelin in cardiac fibrosis post-MI.
• To elucidate the underlying mechanisms involving the Nrf2/NADPH/ROS pathway.
• To evaluate ghrelin's effects on cardiac function, fibrosis, and oxidative stress in vivo and in vitro.

Main Methods:

• Utilized a rat model of myocardial infarction (MI) and Angiotensin II (Ang II)-stimulated cardiac fibroblasts (CFs).
• Administered ghrelin and assessed cardiac function, fibrosis markers, and oxidative stress markers.
• Investigated the effects of ghrelin receptor inhibition (d-Lys3-GHRP-6) and Nrf2 knockdown in CFs.
• Characterized the expression profiles of Nrf2, fibrosis markers, NADPH oxidase, and ROS.

Main Results:

• Ghrelin administration improved cardiac function and reduced cardiac fibrosis after MI.
• Ghrelin upregulated Nrf2 expression while downregulating fibrotic proteins, NADPH oxidase, and ROS production.
• In vitro, ghrelin attenuated Ang II-induced CF migration, proliferation, and oxidative stress.
• Inhibition of ghrelin receptors or Nrf2 abolished the protective effects of ghrelin.

Conclusions:

• Ghrelin ameliorates cardiac fibrosis following MI and Ang II stimulation.
• Ghrelin exerts cardioprotection by activating the Nrf2 pathway, which subsequently inhibits the NADPH/ROS pathway.
• Ghrelin represents a potential therapeutic target for managing cardiac fibrosis and improving post-MI outcomes.