Cell contractility and focal adhesion kinase control circumferential arterial stiffness

Area of Science:

• Cardiovascular Biology
• Biomedical Engineering
• Mechanobiology

Background:

• Arterial stiffening is a key feature of aging and cardiovascular disease.
• Vascular smooth muscle cells (SMCs) influence arterial stiffness through extracellular matrix remodeling, but their direct roles in contractility and mechanosensing remain unclear.
• Understanding SMC contributions to arterial pressure response is crucial for biomedical applications.

Purpose of the Study:

• To investigate the direct contributions of SMC contractility and focal adhesion kinase (FAK) to arterial stiffness and pressure response.
• To elucidate the mechanisms by which SMCs regulate arterial mechanics.

Main Methods:

• Pressure myography of intact carotid arteries in mice.
• Pharmacologic inhibition of SMC contractility (blebbistatin, EGTA).
• Genetic deletion of SMC focal adhesion kinase (FAK) and assessment of arterial mechanics via biaxial inflation-extension tests.

Main Results:

• Acute inhibition of SMC contractility reduced arterial stiffness, predominantly in the circumferential direction.
• Genetic deletion of SMC FAK attenuated arterial contraction, reduced vessel wall thickness, and decreased circumferential arterial stiffness.
• The effects of FAK deletion were abolished by inhibiting contractility, indicating a link between FAK, contractility, and stiffness.

Conclusions:

• SMC contractility and FAK are critical regulators of arterial wall thickness and directional arterial stiffening.
• These findings highlight novel mechanisms linking cellular mechanics to vascular structure and function.
• Targeting SMC contractility and FAK may offer therapeutic strategies for managing arterial stiffening.