华中科技大学
同济医学院病理系
阮秋蓉
血管祖细胞在动脉粥样硬化发病中的作用
Vascular Progenitor Cells Contribute to Pathogenesis of Atherosclerosis
Accumulation of smooth muscle cells (SMCs) plays a principal role in atherogenesis
It generally is believed that neointimal SMCs in vascular lesions originate locally from SMCs of the medial layer.
However, several phenomena could not be explained by this hypothesis.
preface
Very few articles have documented SMCs migrating across the internal elastic lamina from the media into the subendothelial layer. Blood cells attach to the luminal side of the injured artery prior to the development of neointimal hyperplasia.
Neointima could be formed in the absence of medial cells.
SMC hyperplasia could be prevented by blocking chemokines or adhesion molecules, which play a crucial role in recruiting blood cells but have no effect on migration and proliferation of differentiated SMCs.
Neointimal SMCs are quite distinct from medial SMCs in phenotype and gene expression patterns.
Some of the SMC-like cells in vascular lesions are derived from blood cells rather than from medial cells.
Hypothesis
Express various markers for SMCs
心脏移植
These results indicated
that the majority of the neointimal
cells derived from the recipient cells,
but not from the medial cells of donor origin.
源于受者细胞
骨髓移植
These results indicated
that bone marrow cells give rise to vascular
cells, thereby contributing to arterial
remodeling after mechanical injury.
源于骨髓细胞
These results indicate that bone marrow cells give rise to SMC-like cells observed in hyperlipidemia-induced atherosclerotic plaques.
高脂致AS斑块中SMC样细胞源于骨髓
骨髓多能细胞（Pluripotent cells）
造血干细胞（hematopoietic stem cells ，HSCs)
间叶干细胞（mesenchymal stem cells）
HSC (c-Kit, Sca-1, Lin) was isolated from the bone marrow of LacZ mice
3,000 cells were injected into lethally irradiated wild-type mice (LacZ) -.
Four weeks after bone marrow reconstitution, the femoral arteries of the recipient mice were injured mechanically
At 4 weeks, the injured arteries showed neointimal hyperplasia.
The neointima and the media contained many LacZ-positive cells. Some LacZ positive cells expressed α-SMA. Some LacZ positive cells expressed CD31.
These findings indicate that the c-Kit, Sca-1,Lin fraction of bone marrow cells has the potential to differentiate into either SMCs or ECs, thereby contributing to vascular remodeling.
血管祖细胞
造血干细胞
血管重塑
Smooth muscle progenitor cells
Endothelial progenitor cell
治疗靶点
内皮祖细胞参与出生后的血管发生和缺血组织的血管新生，参与损伤血管内皮的修复。
血管内皮损伤是AS发生的始动因素。冠心病患者外周血内皮祖细胞的数量减少，功能减退。
内皮祖细胞有可能通过对损伤血管内皮的修复，抑制AS的发生。
谢谢！