5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside reduces intimal hyperplasia of tissue engineering blood vessel by inhibiting phenotype switch of vascular smooth muscle cell.
5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside reduces intimal hyperplasia of tissue engineering blood vessel by inhibiting phenotype switch of vascular smooth muscle cell.
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DOI：
10.1002/jbm.b.33585
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发表时间：
2017-05
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影响因子：
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通讯作者：
Yangxiao Wu;Ge Liu;Wen Chen;Mingcan Yang;Chuhong Zhu
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文献类型：
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作者：
Yangxiao Wu;Ge Liu;Wen Chen;Mingcan Yang;Chuhong Zhu
内膜增生（IH）是血管移植和血管内支架植入患者临床失败的原因。血管平滑肌细胞（VSMCs）的增殖和表型转换在IH中起重要作用。抑制VSMCs的增殖，维持VSMCs的分化表型是减少IH的一种方法。本文通过药物筛选，将5-氨基咪唑-4-甲酰胺1-β-D-呋喃核糖苷（AICAR）用于实验。结果发现，AICAR处理后，VSMCs的代谢、自噬和分化能力增强，这对VSMCs的正常功能具有重要意义，但VSMCs的分泌能力降低。MTT法、EdU法和细胞周期分析显示AICAR可诱导VSMCs细胞周期阻滞于G1期，抑制VSMCs增殖。采用大鼠颈总动脉血管移植模型评价AICAR的体内功能。AICAR修饰的组织工程血管（TEBV）比对照TEBV具有更高的通畅率和更少的IH。结论：AICAR通过促进VSMCs的代谢和自噬，改善VSMCs的正常功能，抑制VSMCs的增殖、旁分泌和表型转换，进而降低TEBV中的IH。© 2016 Wiley Periodicals，Inc. J Biomed Mater Res Part B：Appl Biomater，105 B：744-752，2017。
Intimal hyperplasia (IH) is the cause of clinical failure in patients with vascular transplants and intravascular stents. The proliferation and phenotype switching of vascular smooth muscle cells (VSMCs) play important roles in IH. Inhibiting the proliferation of VSMCs and maintaining the differentiated phenotype of VSMCs is one way to reduce IH. In this article, 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) was used in experiments after drug screening. We found that the metabolism, autophagy, and differentiation of VSMCs were enhanced which were important to the normal function of VSMCs, but the secretion of VSMCs was reduced after AICAR treatment. AICAR induces G1 phase arrest and inhibits the proliferation of VSMCs using the MTT and EdU assays and cell cycle analysis. Then, the rat carotid artery vessel transplantation model was used to evaluate the function of AICAR in vivo. AICAR-modified tissue-engineered blood vessels (TEBVs) had a higher patency rate and less IH than the control TEBVs. In conclusion, AICAR can improve the normal function of VSMCs by increasing the metabolism and autophagy of VSMCs but inhibit the proliferation, paracrine, and phenotypes switching of VSMCs, further contribute the reducing of IH in TEBVs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 744-752, 2017.