Investigating the NF-κB signaling pathway in heart failure: Exploring potential therapeutic approaches

Heart failure (HF) syndrome is of great interest as an emerging epidemic. Due to the increasing elderly population worldwide, the total number of HF patients is increasing every day. This disease places a significant economic burden on the healthcare and treatment systems of developing societies, and this situation is very concerning. Despite many advances in the diagnosis and treatment of cardiovascular diseases, HF is still the main cause of death worldwide. This clinical syndrome has many cellular and molecular complications, which are often aggravated by increased levels of pro-inflammatory cytokines, which lead to adverse clinical outcomes. Nuclear factor kappa B (NF-κB), a pivotal family of transcription factors, plays a crucial role in various biological processes, particularly in inflammation, immune response, cell proliferation, and cell survival. Studies show that the NF-κB signaling pathway plays a role in modulating cardiac regeneration, apoptosis, and myocardial fibrosis. It has been found that the NF-κB signaling pathway can affect heart function and HF through the regulation of matrix metalloproteinases and fibrotic mediators. Also, the NF-κB pathway regulates cell activities in cardiac cardiomyocytes and regulates the function of this organ by establishing a precise interaction between apoptosis and pyroptosis. However, the exact molecular mechanisms of this influence have not been well defined and there are many scientific gaps in this matter. This review tries to highlights potential therapeutic strategies to target NF-κB, including the use of anti-inflammatory agents and genetic modulation, which may provide new ways to reduce cardiac fibrosis and improve outcomes in HF patients. Certainly, increasing understanding of the multifaceted role of NF-κB in HF can lead to innovative treatments aimed at reducing the growing number of patients worldwide.