Schachner Thomas, Zou Yping, Oberhuber Alexander, Mairinger Thomas, Tzankov Alexandar, Laufer Günther, Ott Harald, Bonatti Johannes
Department of Cardiac Surgery, Innsbruck University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria.
Eur J Cardiothorac Surg. 2004 Apr;25(4):585-90. doi: 10.1016/j.ejcts.2003.07.013.
C-type natriuretic peptide (CNP), which is produced by vascular endothelial cells, exhibits anti-proliferative and anti-inflammatory effects. Cytotoxic T-lymphocytes may be involved in vein graft disease. Attenuation of vein graft disease necessitates a remodelling of the arterialized vein towards a more contractile phenotype which is characterized, among other factors, by the calponin amount. We investigated the effects of perivascularly applied CNP in a mouse model of vein graft disease.
C57BL6J mice underwent interposition of the inferior vena cava from isogenic donor mice into the common carotid artery using a previously described cuff technique. In the treatment group, 10(-6)mol/l of CNP were applied locally in pluronic gel. The control group did not receive local treatment. Grafts were harvested at 1, 2, 4, and 8 weeks and underwent morphometric analysis as well as immunohistochemical analysis.
In grafted veins without treatment (controls) median intimal thickness was 10 (6-29), 12 (8-40)microm, was 47 (12-58), and 79 (62-146)microm after 1, 2, 4 and 8 weeks, respectively. In the treatment groups, which received 10(-6)mol/l of CNP, the intimal thickness was 5 (3-6), 6 (4-15), 32 (5-54), and 43 (39-70)microm after 1, 2, 4 and 8 weeks, respectively. This reduction of intimal thickness was significant at 1, 2 and 8 weeks. Immunohistochemically, the reduction of intimal thickness was associated with a decreased infiltration of CD-8 positive cells and an increased amount of calponin in the CNP-treated grafts.
We conclude that perivascular application of CNP inhibits neointimal hyperplasia of vein grafts in a mouse model. These results suggest that CNP may have a therapeutic potential for the prevention of vein graft disease.
由血管内皮细胞产生的C型利钠肽（CNP）具有抗增殖和抗炎作用。细胞毒性T淋巴细胞可能参与静脉移植物疾病。减轻静脉移植物疾病需要将动脉化静脉重塑为更具收缩性的表型，其中一个特征因素是钙调蛋白的含量。我们研究了在静脉移植物疾病小鼠模型中血管周围应用CNP的效果。
使用先前描述的套管技术，将同基因供体小鼠的下腔静脉插入C57BL6J小鼠的颈总动脉。在治疗组中，将10⁻⁶mol/l的CNP局部应用于普朗尼克凝胶中。对照组未接受局部治疗。在1、2、4和8周时采集移植物，进行形态计量分析和免疫组织化学分析。
未经治疗的移植静脉（对照组）在1、2、4和8周后的内膜中值厚度分别为10（6 - 29）、12（8 - 40）微米、47（12 - 58）微米和79（62 - 146）微米。在接受10⁻⁶mol/l CNP的治疗组中，1、2、4和8周后的内膜厚度分别为5（3 - 6）、6（4 - 15）、32（5 - 54）和43（39 - 70）微米。内膜厚度的这种减少在1、2和8周时具有统计学意义。免疫组织化学显示，内膜厚度的减少与CNP处理的移植物中CD - 8阳性细胞浸润减少和钙调蛋白含量增加有关。
我们得出结论，在小鼠模型中血管周围应用CNP可抑制静脉移植物的内膜增生。这些结果表明CNP可能具有预防静脉移植物疾病的治疗潜力。
