HAPLN1 knockdown inhibits heart failure development via activating the PKA signaling pathway

Area of Science:

• Molecular biology
• Cardiovascular research
• Biomedical science

Background:

• Heart failure (HF) is a widespread, complex condition with unclear molecular underpinnings.
• Millions worldwide are affected by heart failure, imposing significant health and economic burdens.
• Understanding the molecular mechanisms of HF pathogenesis is crucial for developing effective treatments.

Purpose of the Study:

• To identify key genes involved in heart failure pathogenesis using bioinformatics.
• To investigate the functional role of HAPLN1 in Angiotensin II-induced AC16 cells and a rat model of HF.
• To elucidate the molecular pathways regulated by HAPLN1 in HF.

Main Methods:

• Bioinformatic screening identified key HF-related genes, including HAPLN1.
• In vitro experiments assessed HAPLN1 knockdown effects on Angiotensin II-treated AC16 cells, measuring oxidative stress and apoptosis.
• An in vivo HF rat model was established to evaluate HAPLN1's impact on cardiac function and histology, alongside pathway analysis via western blot.

Main Results:

• HAPLN1 was identified as an overexpressed gene in HF, with its knockdown improving cell viability and reducing apoptosis in vitro.
• In a rat HF model, HAPLN1 knockdown improved echocardiographic indices (LVEF, LVFS) and reduced cardiac remodeling (LVESV).
• HAPLN1 knockdown modulated oxidative stress markers (increased GSH, decreased MDA, LDH) and inflammatory factors (decreased TNF-α, IL-6), activating the PKA pathway.

Conclusions:

• HAPLN1 knockdown demonstrates a protective effect against HF progression.
• The mechanism involves the activation of the PKA pathway, suggesting a novel therapeutic target.
• These findings provide new insights for the clinical management of heart failure.