Silencing fatty acid-binding protein 4 improved sepsis-induced myocardial dysfunction through anti-apoptotic and antioxidant effects by mammalian target of rapamycin signaling pathway.

in CytoJournal by Zhilei Qiu, Kexing Zhou, Qinyao Qi, Wei Chen

TLDR

  • The study investigated the role of FABP4 in Sepsis-Induced Myocardial Dysfunction (SIMD) and found that silencing FABP4 expression alleviated SIMD through the mTOR signaling pathway.
  • The study's key insights include the potential therapeutic application of FABP4 silencing for SIMD and the involvement of the mTOR signaling pathway in FABP4-mediated SIMD.

Abstract

One of the main complications of sepsis that is linked to poor clinical outcomes and high mortality is sepsis-induced myocardial dysfunction (SIMD). Fatty acid-binding protein 4 (FABP4) is a protein that is expressed in macrophages and adipose tissue and is involved in inflammation and apoptosis in various pathological processes. The purpose of this study was to investigate the role of FABP4 in SIMD. The H9c2 cell model of myocardial dysfunction induced by septicemia was established by lipopolysaccharide (LPS). Measurements of cell viability, apoptosis, reactive oxygen species levels, mitochondrial activity, and proinflammatory factor expression were used to assess FABP4's involvement in SIMD. In addition, the expression level of key proteins in the mammalian target of rapamycin (mTOR) signaling pathway was analyzed using Western blot. Finally, the combination of AZD-8055 further demonstrated the possibility of mTOR as a therapeutic target for SIMD. Silencing FABP4 expression drastically increased H9c2 cell viability and mitochondrial function. In addition, by upregulating B-cell lymphoma-2 (Bcl-2) and downregulating Bcl-2 associated X protein, FABP4 silencing improved LPS-induced anti-apoptosis of H9c2 cells. Finally, silencing FABP4 alleviated SIMD through the mTOR signaling pathway. However, the therapeutic effect was inhibited when FABP4 silencing was combined with the mTOR inhibitor AZD-8055. Silencing FABP4 alleviates LPS-induced inflammatory response and apoptosis in H9c2 cells and enhances mitochondrial function through the mTOR signaling pathway.

Overview

  • The study aimed to investigate the role of Fatty acid-binding protein 4 (FABP4) in Sepsis-Induced Myocardial Dysfunction (SIMD).
  • The researchers used the H9c2 cell model to induce myocardial dysfunction through septicemia and measured cell viability, apoptosis, reactive oxygen species levels, mitochondrial activity, and proinflammatory factor expression.
  • The study found that silencing FABP4 expression improved cell viability, mitochondrial function, and alleviated SIMD through the mammalian target of rapamycin (mTOR) signaling pathway.

Comparative Analysis & Findings

  • Silencing FABP4 expression significantly increased H9c2 cell viability and mitochondrial function compared to control cells.
  • FABP4 silencing improved LPS-induced anti-apoptosis of H9c2 cells by upregulating B-cell lymphoma-2 (Bcl-2) and downregulating Bcl-2 associated X protein.
  • The combination of FABP4 silencing and mTOR inhibitor AZD-8055 inhibited the therapeutic effect on SIMD.

Implications and Future Directions

  • The study suggests that FABP4 may be a potential therapeutic target for SIMD, and silencing its expression may alleviate SIMD through the mTOR signaling pathway.
  • Future studies should investigate the underlying mechanisms of FABP4-mediated SIMD and explore the possibility of combining FABP4 silencing with other therapeutic approaches.
  • The significance of this study lies in its potential to develop novel therapeutic strategies for SIMD, which is a major complication of sepsis and is associated with high mortality.
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