Vascular smooth muscle cell mechanotransduction: Pathways, phenotypes and emerging technologies

Area of Science:

• Vascular biology
• Mechanobiology
• Cardiovascular disease research

Background:

• Vascular smooth muscle cells (VSMCs) are crucial for vascular integrity and disease progression.
• Mechanobiology research has largely overlooked VSMC mechanosensing and bioenergetic reprogramming.
• VSMC phenotypic transitions are linked to metabolic changes, a dimension not fully explored in mechanobiology.

Purpose of the Study:

• To synthesize current knowledge on VSMC mechanobiology across mechanical microenvironment, phenotypic plasticity, and mechanosensing pathways.
• To explore emerging technologies like organ-on-a-chip platforms for studying VSMC mechanobiology.
• To introduce a novel framework linking VSMC mechanotransduction, metabolic reprogramming, and atherogenesis.

Main Methods:

• Literature review synthesizing VSMC mechanobiology research.
• Discussion of emerging technologies for mechanobiology research.
• Development of an integrated framework for mechano-metabolic signaling in VSMCs.

Main Results:

• VSMCs sense diverse mechanical stimuli (stretch, shear stress, stiffness, pressure) via specialized sensors.
• Dysregulated VSMC mechanotransduction contributes to hypertension, atherosclerosis, and arterial stiffening.
• A novel mechano-metabolic signaling framework positions VSMCs as central to cardiovascular disease pathogenesis.

Conclusions:

• VSMC mechanobiology, including their metabolic reprogramming, is a critical, underexplored area in cardiovascular disease.
• Mechano-metabolic signaling represents a promising therapeutic target for cardiovascular diseases.
• Further research using advanced technologies is needed to fully elucidate VSMC mechanobiology.