Iwata Hiroshi, Sata Masataka
Department of Cardiovascular Medicine, University of Tokyo Graduate School Medicine, Tokyo, Japan.
Front Biosci. 2007 May 1;12:4157-67. doi: 10.2741/2377.
Atherosclerosis is responsible for more than half of all deaths in western countries. Numerous studies have reported that exuberant accumulation of smooth muscle cells (SMCs) plays a principal role in the pathogenesis of occlusive vascular diseases. It has been assumed that SMCs derived from the adjacent medial layer migrate towards the atherosclerotic lesion, proliferate and synthesize extracellular matrix, thus contributing to atheroma growth. Although much effort has been devoted to targeting the migration and proliferation of medial SMCs, no effective therapy to prevent occlusive vascular remodeling has been established. By taking advantage of genetically-modified mice, we recently reported that bone marrow cells substantially contribute to the pathogenesis of vascular diseases. It was suggested that bone marrow cells may have the potential to give rise to vascular progenitor cells that home in the damaged vessels and differentiate into smooth muscle cells or endothelial cells, thereby contributing to vascular repair, remodeling, and lesion formation. This article summarizes what we learned from genetically-modified animals regarding the origins and the fates of vascular cells that contribute to lesion formation.
在西方国家，超过半数的死亡由动脉粥样硬化导致。大量研究报告指出，平滑肌细胞（SMC）的过度积聚在闭塞性血管疾病的发病机制中起主要作用。据推测，源自相邻中层的SMC向动脉粥样硬化病变迁移、增殖并合成细胞外基质，从而促进动脉粥样瘤生长。尽管人们在针对中层SMC的迁移和增殖方面付出了诸多努力，但尚未建立有效的预防闭塞性血管重塑的治疗方法。利用基因修饰小鼠，我们最近报告称骨髓细胞在血管疾病的发病机制中起重要作用。有人提出，骨髓细胞可能具有产生血管祖细胞的潜力，这些祖细胞归巢到受损血管并分化为平滑肌细胞或内皮细胞，从而促进血管修复、重塑和病变形成。本文总结了我们从基因修饰动物中了解到的关于促成病变形成的血管细胞的起源和命运的知识。
