血管細胞の形態変換とマトリックス

抄録

Human arteries have areas that are preferential or resistant to atherosclerosis. The preferential sites include the proximal and outer walls of the branchings which are subject to low shear stress, while the resistant areas include an apical portion of the flow dividers of the branchings, which is subject to laminar high shear stress.
Electron microscopic studies revealed that synthetic intimal smooth muscle cells (I-SMC) were distributed in the intima of the preferential site which is rich in GAGs. However, most of the I-SMC in the resistant areas was located in the contractile, which is found in the collagenous intima even in youth.
In order to clarify the mechanisms of phenotypic changes in the I-SMC of both regions, the following in vitro studies were carried out.
1) Endothelial cells (EC) were exposed to a constant laminar shear stress of 10 dynes/cm² for up to 24 hours. Conditioning media (CM) of the EC exposed to shear stress were applied to the SMC which were cultivated in other dishes. Collagen synthesis of SMCs under CM was studied. CM for 2 to 8 hours augmented collagen synthesis in proportion to the exposure time of EC to shear stress. The collagen types produced were I, III and V. The production of type III by SMC increased in proportional to the amount of time EC was exposed to shear stress.
2) The effects of collagen types I and III on phenotype and the proliferation of SMCs were assessed for the respective collagen gels. Type III collagen caused a change in phenotype (from synthetic to contractile) and suppressed the DNA synthesis of SMC, while type I collagen caused no changes.
These results suggest that a laminar high shear stress can stimulate EC to secrete some effective substances and promote collagen synthesis of the underlying SMC. The growth of SMC surrounded by collagen fibers in the intima (particularly type III) was suppressed. These experimental results may explain the mechanisms by which laminar shear stress makes the arterial wall resistant to atherogenesis.