Inhibition of arterial cells proliferation in vivo in injured arteries by hyaluronan fragments
Inhibition of arterial cells proliferation in vivo in injured arteries by hyaluronan fragments
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DOI：
10.1016/s0021-9150(03)00303-4
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发表时间：
2003-11-01
期刊：
影响因子：
5.3
通讯作者：
Levesque, H
中科院分区：
文献类型：
--
作者：
Chajara, A;Raoudi, M;Levesque, H
先前已经证明，给大鼠施用高水平的高分子透明质酸（透明质酸，HA）能够显着减少受损动脉中新内膜的形成。在本研究中，我们的目的是验证小形式的HA（4-16糖）是否仍然能够减少ASMC对主动脉损伤的增殖反应。治疗大鼠总共接受8次固定剂量HA片段注射（550μl体积中含有27mg/kg大鼠）。在球囊导管损伤 (BCI) 当天进行两次注射：一次是在 BCI 前 10 分钟进行静脉注射，另一次是在 BCI 后立即进行皮下注射。其他注射（皮下）是在 BCI 后第 2、4、6、8、10 和 12 天进行。对照大鼠接受等体积的仅含有透明质酸酶的溶解缓冲液，该缓冲液在注射给大鼠之前已被破坏。 BCI 后 14 天分析新内膜形成。与对照组相比，接受HA片段的大鼠的内膜中层湿重和DNA含量显着降低（湿重2P = 0.01，DNA 0.03）。这一发现得到了组织形态计量学研究的证实，该研究表明，治疗大鼠的新内膜面积和新内膜/新内膜+中膜的比率均显着下降（内膜面积2P = 0.03，比率0.049）。因此，我们的数据首次表明，给予极低分子量（4-16 糖）的 HA 片段可减少主动脉对体内损伤的增殖反应。总之，HA 片段作为具有良好安全性的成分，可能为预防血管成形术后再狭窄带来希望。 (C) 2003 Elsevier Ireland Ltd. 保留所有权利。
It has been demonstrated previously that administration of high levels of high molecular mass hyaluronan (hyaluronic acid, HA) to rats was able to reduce in a significant way neointima formation in the injured arteries. In the present study, our aim was to verify whether small forms of HA (4-16 saccharides) are still able to reduce the proliferative response of ASMC to aortic injury. Treated rats received a total of 8 injections of a fixed dose of HA fragments (27 mg/kg rat contained in a volume of 550 mul). Two injections were given on the day of balloon catheter injury (BCI): one, intravenous, 10 min before BCI and one, subcutaneous, immediately after the BCI. The others injections (subcutaneous) were at 2, 4, 6, 8, 10 and 12 days after BCI. Control rats received an equivalent volume of the dissolving buffer containing only hyaluronidase, which has been destroyed before injection to rats. Neointima formation was analysed 14 days after the BCI. Intima-media wet weight and DNA content were significantly reduced in rats receiving HA fragments in comparison to controls (2P = 0.01 for wet weight and 0.03 for DNA). This finding was confirmed by the histomorphometric study which showed that both neointima area and the ratio neointima/neointima + media were significantly decreased in treated rats (2P = 0.03 for intima area and 0.049 for the ratio). Our data showed thus and for the first time that administration of HA fragments with a very low molecular mass (4-16 saccharides) reduces the proliferative reaction of aorta to injury in vivo. In conclusion, HA fragments, which are components with an excellent safety profile, may offer hope for the prevention of restenosis after angioplasty. (C) 2003 Elsevier Ireland Ltd. All rights reserved.