LDL‑induced NLRC3 inflammasome activation in cardiac fibroblasts contributes to cardiomyocytic dysfunction

Area of Science:

• Cardiovascular Biology
• Inflammation Research
• Cellular Signaling

Background:

• Heart failure (HF) is a progressive myocardial disease where chronic inflammation plays a critical role in cardiac dysfunction.
• Cardiac fibroblasts (CFs) are the predominant cell type in the cardiac microenvironment, and their role in HF progression is significant.
• Proper communication between cardiomyocytes and CFs is vital for maintaining cardiac function.

Purpose of the Study:

• To investigate the role of cardiac fibroblasts (CFs) in the progression of heart failure (HF).
• To elucidate the molecular mechanisms underlying the pro-inflammatory phenotype of CFs in HF.
• To explore the potential of targeting specific pathways in CFs for therapeutic benefit in HF.

Main Methods:

• ELISAs were used to quantify inflammatory factors in the sera of HF patients.
• Pearson's correlation coefficient was employed to analyze the association between inflammatory factors and CF activation.
• Western blotting was utilized to investigate the molecular mechanisms of CF pro-inflammatory activation.

Main Results:

• Serum levels of Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) were significantly elevated in HF patients.
• Cardiac fibroblasts in HF patients exhibited extensive activation and released excessive cytokines, impairing cardiomyocyte viability.
• Low-density lipoprotein (LDL)-induced activation of the NLRC3 inflammasome in CFs led to pro-inflammatory phenotypes.

Conclusions:

• CF-derived microenvironmental inflammation, driven by LDL-induced inflammasome activation, suppresses cardiomyocyte viability in HF.
• Targeting LDL within CFs demonstrated a therapeutic potential by improving cardiomyocyte function and inhibiting apoptosis.
• This study establishes a cellular basis for CF activation in HF and highlights cellular interactions crucial for HF treatment.