Vascular Mechanobiology: From Membrane to Nucleus

Area of Science:

• Cardiovascular Biology
• Cellular Mechanobiology
• Biophysics

Background:

• Vascular cells, including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), are constantly subjected to hemodynamic forces like shear stress and cyclic stretch.
• Abnormal mechanical forces are implicated in cardiovascular diseases such as atherosclerosis, hypertension, and vein graft disease, driving vascular dysfunction and remodeling.
• These forces initiate signaling cascades through membrane mechanosensors, but the role of the nucleus is increasingly recognized.

Purpose of the Study:

• To review the role of mechanosensors on the vascular cell membrane.
• To highlight the emerging functions of nuclear components in hemodynamic force-mediated vascular remodeling.
• To provide insights into the molecular mechanisms of vascular homeostasis and disease.

Main Methods:

• Literature review focusing on mechanotransduction in vascular cells.
• Summary of known membrane-associated mechanosensors.
• Emphasis on the role of nuclear envelope proteins, nuclear pore complex, and chromatin in mechanosensing.

Main Results:

• Hemodynamic forces activate cellular signaling pathways.
• Nuclear components, including the nuclear envelope, NPC, and chromatin, are identified as critical mechanosensitive elements.
• These nuclear elements modulate chromatin dynamics and gene transcription in response to mechanical stress.

Conclusions:

• The nucleus is a crucial player in vascular mechanotransduction, influencing chromatin dynamics and gene expression.
• Understanding nuclear mechanosensing is vital for elucidating vascular physiological and pathophysiological remodeling.
• This knowledge may pave the way for novel hemodynamic-based therapeutic strategies for vascular diseases.