Cyclic stretch of embryonic cardiomyocytes increases proliferation, growth, and expression while repressing Tgf-β...

Area of Science:

• Cardiovascular Biology
• Developmental Biology
• Biophysics

Background:

• Congenital heart defects, including Hypoplastic Left Heart Syndrome (HLHS), are linked to abnormal biomechanical stimuli during embryonic development.
• The molecular mechanisms by which embryonic cardiomyocytes respond to mechanical forces, such as stretch, are not fully understood.

Purpose of the Study:

• To investigate the molecular and phenotypic responses of embryonic mouse cardiomyocytes (EMCMs) to cyclic mechanical stretch.
• To elucidate the role of biomechanical stimuli in cardiac development and pathogenesis.

Main Methods:

• Exposure of EMCMs to cyclic stretch.
• RNA-Sequencing analysis to identify modulated gene ontology groups.
• Assessment of EMCM proliferation, size, gene expression, and protein levels.
• Investigation of Transforming Growth Factor-β (Tgf-β) signaling pathway activity.
• Functional assays using dynamic monolayer force microscopy (DMFM).

Main Results:

• Cyclic stretch significantly modulated gene ontology groups related to myofibril and cardiac development.
• Stretch increased EMCM proliferation, size, cardiac gene expression, and myofibril protein content.
• Stretch repressed Tgf-β signaling components, including gene and protein expression.
• Inhibition of Tgf-β signaling promoted EMCM size and repressed proliferation and contractile function.

Conclusions:

• Biomechanical stimuli are vital regulators of embryonic cardiomyocyte proliferation, growth, and function.
• The Transforming Growth Factor-β (Tgf-β) pathway is a key mediator through which mechanical forces influence cardiac development.
• Understanding these biomechanical pathways is critical for addressing congenital heart defects like HLHS.