Sympathetic-like-integrated engineered heart tissue models AGEs-induced adverse remodeling

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Neuroscience

Background:

• Cardiovascular metabolic diseases (CMDs) are a leading cause of death, but their mechanisms are poorly understood.
• Current in vitro models, like engineered heart tissues (EHTs), lack neural components and cannot fully replicate complex neuro-cardiac interactions crucial for CMDs.

Purpose of the Study:

• To develop a novel neuron-like-Integrated Engineered Heart Tissue (SIEHT) for studying neuro-cardiac interactions.
• To provide an advanced tool for investigating physiological and pathological conditions in CMD research.

Main Methods:

• Constructed Sympathetic-like-Integrated Engineered Heart Tissue (SIEHT) by integrating sympathetic-like neurons into EHT.
• Compared SIEHT and conventional EHT structural/functional properties using morphological, molecular, and contractility analyses.
• Assessed AGEs-induced pathological remodeling in SIEHT via cell viability, oxidative stress, contractility, and transcriptomics.

Main Results:

• SIEHT showed enhanced structural and functional maturation compared to EHT, with better cardiomyocyte alignment and contractility.
• Pathological conditions (AGEs) induced more severe dysfunction, neural injury, and abnormal beating in SIEHT.
• Transcriptomic analysis revealed enriched AGE-RAGE signaling pathways relevant to diabetic complications.

Conclusions:

• Successfully developed a novel SIEHT model that replicates physiological neuro-cardiac interactions.
• The SIEHT model effectively recapitulates adverse remodeling in response to AGEs, offering insights into CMD pathophysiology.
• This innovative model serves as a powerful tool for understanding neuro-cardiac dysregulation in cardiovascular metabolic diseases.