INDUCTION OF ANGIOTENSIN-CONVERTING ENZYME IN THE NEOINTIMA AFTER VASCULAR INJURY - POSSIBLE ROLE IN RESTENOSIS
INDUCTION OF ANGIOTENSIN-CONVERTING ENZYME IN THE NEOINTIMA AFTER VASCULAR INJURY - POSSIBLE ROLE IN RESTENOSIS
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DOI：
10.1172/jci116965
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发表时间：
1994-01-01
影响因子：
15.9
通讯作者：
PRATT, RE
中科院分区：
文献类型：
--
作者：
RAKUGI, H;KIM, DK;PRATT, RE
血管紧张素II（AngII）促进血管平滑肌细胞的生长。与此相一致，血管紧张素II增强血管损伤后体内新生内膜增殖，而血管紧张素转换酶（ACE）抑制剂减弱这一过程。由于组织ACE在局部血管紧张素II产生的控制中起着关键作用，我们研究了血管损伤是否导致血管ACE表达增加，这可能导致血管紧张素II产生增加。用2French球囊导管损伤Sprague-Dawley大鼠的腹主动脉。分析损伤和未损伤主动脉的形态计量学变化、ACE酶活性和ACE免疫组织化学定位。血管ACE活性在损伤的主动脉显着高于在未损伤的主动脉，而血清和肺ACE水平在两组之间没有差异。ACE蛋白在新生内膜中的细胞分布与α平滑肌肌动蛋白相似，但与内皮（血管性血友病因子）或单核细胞/巨噬细胞（艾德-1）标记物不同，表明ACE在新生内膜平滑肌细胞中表达。这些数据表明，血管损伤导致血管ACE的诱导，并表明血管ACE的抑制可能是重要的，在预防球囊损伤后再狭窄。
Angiotensin II (Ang II) promotes growth of vascular smooth muscle cells in vitro. Consistent with this, Ang II enhances neointimal proliferation in vivo after vascular injury, while angiotensin converting enzyme (ACE) inhibitors attenuate this process. Since tissue ACE plays a key role in the control of local Ang II production, we examined whether vascular injury resulted in an increase in vascular ACE expression that may result in increased Ang II production. Abdominal aorta of Sprague-Dawley rats were injured with a 2 French balloon catheter. Morphometrical changes, ACE enzymatic activity, and localization of ACE by immunohistochemistry in injured and uninjured aorta were analyzed. Vascular ACE activity in the injured aorta was significantly higher than in the uninjured aorta, while serum and lung ACE levels were not different between the two groups. The cellular distribution of the ACE protein in the neointima was similar to that of alpha smooth muscle actin but differed from those of endothelial (von Willebrand factor) or monocytes/macrophages (ED-1) markers, demonstrating that ACE was expressed in neointimal smooth muscle cells. These data demonstrate that vascular injury results in the induction of vascular ACE and suggest that the inhibition of vascular ACE may be important in the prevention of restenosis after balloon injury.