Remodeling of autologous saphenous vein grafts - The role of perivascular myofibroblasts

被引:161
作者
Shi, Y
OBrien, JE
Mannion, JD
Morrison, RC
Chung, WS
Fard, A
Zalewski, A
机构
[1] THOMAS JEFFERSON UNIV,CARDIOVASC RES CTR,DIV CARDIOL,DEPT MED CARDIOL,PHILADELPHIA,PA 19107
[2] THOMAS JEFFERSON UNIV,DEPT SURG CARDIOTHORAC SURG,PHILADELPHIA,PA 19107
关键词
atherosclerosis; bypass; myofibroblast; remodeling; veins;
D O I
10.1161/01.CIR.95.12.2684
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Aortocoronary saphenous vein grafts (SVGs) undergo structural changes that render them susceptible to atherosclerosis. Accordingly, the origin of neointimal hyperplasia was examined in porcine arterialized SVGs to determine the mechanism of vein graft remodeling. Methods and Results At 2 to 4 days after surgery, the percentage of cells lacking differentiation markers characteristic for smooth muscle (SM) cells (ie, a alpha-SM actin, desmin, and SM myosin) increased within the media of SVGs interposed in the carotid arteries (P < .001). At 7 to 14 days, these cells acquired a differentiated phenotype (ie, alpha-SM-actin positive/variable desmin/SM-myosin negative) and accumulated in the neointima. At 3 months, the neointima was positive for alpha-SM actin but mostly negative for desmin, which contrasted with medial SMCs that were invariably positive for alpha-SM actin, desmin, and SM myosin. To determine the role of nonmuscle cells in the above process, perivascular wound fibroblasts were selectively labeled and found to translocate through the media of newly placed SVGs, contributing to neointimal formation. These migrating cells differentiated to myofibroblasts exhibiting sustained alpha-SM-actin expression. The intima of human SVGs, retrieved during repeat aortocoronary bypass surgery, exhibited the profile of cytoskeletal proteins that resembled myofibroblasts seen in porcine SVGs. Conclusions Perivascular fibroblasts may infiltrate injured media of arterialized SVGs, differentiate to myofibroblasts (acquiring alpha-SM actin), and contribute to vein graft remodeling. The similarities between porcine and human SVGs regarding the repertoire of cytoskeletal proteins suggest the involvement of myofibroblasts in graft remodeling in the clinical setting.
引用
收藏
页码:2684 / 2693
页数:10
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