Vascular Mechanobiology: From Membrane to Nucleus

The vascular wall is continuously exposed to complex hemodynamic forces in vivo due to blood flow. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) experience distinct mechanical stresses, primarily shear stress and cyclic stretch, which are determined by their spatial organization within the vessel wall. Numerous studies indicate that abnormal (pathological) mechanical forces play crucial roles in EC and VSMC dysfunction during various cardiovascular diseases, including atherosclerosis, hypertension, and vein graft disease. This mechanical dysfunction represents a fundamental driver from vascular homeostasis to pathological remodeling. Hemodynamic forces activate membrane-associated mechanosensors, triggering a cascade of reactions through intricate intracellular signaling networks. Emerging evidence suggests that nuclear components, especially nuclear envelope proteins, nuclear pore complex, and chromatin, serve as important mechanosensitive elements that modulate chromatin dynamics, gene transcription, and ultimately cellular functions. However, research on the role of the nucleus in mechanotransduction remains in its early stages. Here, we briefly summarize the mechanosensors on the vascular cell membrane and particularly focus on the emerging roles of nuclear envelope proteins, nuclear pore complex, and chromatin in hemodynamic force-mediated vascular remodeling. These insights may advance our understanding of the molecular mechanisms underlying both vascular physiological homeostasis and pathophysiological remodeling, potentially leading to novel hemodynamic-based strategies for preventing and treating vascular diseases.