EFFECT OF CONTROLLED ADVENTITIAL HEPARIN DELIVERY ON SMOOTH-MUSCLE CELL-PROLIFERATION FOLLOWING ENDOTHELIAL INJURY
EFFECT OF CONTROLLED ADVENTITIAL HEPARIN DELIVERY ON SMOOTH-MUSCLE CELL-PROLIFERATION FOLLOWING ENDOTHELIAL INJURY
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DOI：
10.1073/pnas.87.10.3773
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
KARNOVSKY, MJ
中科院分区：
文献类型：
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作者：
EDELMAN, ER;ADAMS, DH;KARNOVSKY, MJ
连续静脉输注肝素可抑制内皮损伤后大鼠平滑肌细胞增殖，但可能导致出血和其他并发症。化学修饰的肝素已去除抗凝血特性，但不损失抗增殖作用，但每种化合物的使用仍然受到限制。在这项研究中，在球囊树皮化时，将含有标准肝素和改良肝素的乙烯-醋酸乙烯酯共聚物基质放置在大鼠颈动脉附近。 14天后，定义了平滑肌细胞增殖导致的动脉闭塞。与对照相比，两种肝素化合物的基质递送有效地减少了这种增殖，而不产生全身抗凝或副作用。此外，这种治疗模式似乎比通过静脉泵或放置在远离受伤颈动脉的皮下部位的肝素/聚合物基质施用相同药物更有效。因此，肝素对血管损伤后平滑肌细胞增殖的抑制可能在受损血管壁的微环境中最有效，并且血管成形术和其他血管干预措施后经常出现的加速动脉粥样硬化或再狭窄可能最好采用部位特异性治疗来治疗。
Continuous intravenous infusion of heparin suppresses smooth muscle cell proliferation in rats after endothelial injury but may lead to hemorrhage and other complications. The anticoagulant property has been removed from chemically modified heparin without loss of antiproliferative effect but use of each compounds is still limited. In this study ethylene-vinyl acetate copolymer matrices containing standard and modified heparin were placed adjacent to rat carotid arteries at the time of balloon dendothelialization. After 14 days arterial occlusion by smooth muscle cell proliferation was defined. Matrix delivery of both heparin compounds effectively diminished this proliferation in comparison to controls without producing systemic anticoagulation or side effects. In addition, this mode of therapy appeared more effective than the administration of the same agents by either intravenous pumps or heparin/polymer matrices placed in a subcutaneous site distant from the injured carotid artery. Thus, heparin''s inhibition of smooth muscle cell proliferation after vascular injury might be most effective within the microenvironment of the injured vessel wall, and the accelerated atherosclerosis or restenosis that often follows angioplasty and other vascular interventions might best be treated with site-specific therapy.