血管力学環境を考慮した細胞培養系の確立と細胞内での 力学刺激伝達メカニズムの考察

Abstract

Vascular smooth muscle cells (SMCs) actively remodel arterial wall in which they are exposed to mechanical signals. We recently demonstrated that, in SMCs cultured on a flat normal substrate, actin cytoskeleton has a mechanical connection with the cell nucleus and their internal mechanical signals are transmitted directly to the nucleus. This intracellular force transmission mechanism is important for understanding smooth muscle pathophysiology in diseases such as hypertension and atherosclerosis. However mechanical environments around SMCs in vivo are quite different from those of the cultured cells: they show elongated shape and form a tissue aligned in the circumferential direction of the arterial walls, and they exposed to cyclic tensile stress as a result of the pulse pressure. Thus in this study, we developed cell culture systems based on the mechanical environment of blood vessels: we developed the micro-grooved collagen substrate to induce the elongation and alignment of SMCs like in vivo, and developed a cyclic stretching system for applying the mechanical stimulation. By using this system, we found that morphology of actin cytoskeleton and the nucleus were quite different between the cells cultured on the flat normal substrate and the micro-grooved collagen substrate.