A glycan-based approach to therapeutic angiogenesis.

A glycan-based approach to therapeutic angiogenesis.
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基于聚糖的治疗性血管生成方法。

DOI:
10.1371/journal.pone.0182301
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Kuberan B
Kuberan B
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chua JS;Tran VM;Kalita M;Quintero MV;Antelope O;Muruganandam G;Saijoh Y;Kuberan B

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血管生成是从现有血管系统中长出新血管的过程,涉及多个复杂的生物学过程,是止血、组织愈合和再生的重要步骤。血管生成刺激剂可以改善人类疾病状况,包括肢体缺血、慢性伤口、心脏病和中风。目前提高促血管生成生长因子(包括VEGF和FGF 2)的生物利用度的策略在很大程度上仍然不成功。这项研究表明,小分子,称为点击木糖苷,可以促进血管生成在体外基质胶管形成试验和鸡胚绒毛尿囊膜试验,这取决于他们的苷元部分。木糖苷处理增强网络连接性和细胞存活性,从而在基质胶培养物上维持网络结构延长的时间段。这些作用是通过分泌的木糖苷引发的糖胺聚糖(GAG)链实现的,该链部分通过ERK 1/2介导的信号传导途径起作用。通过在内皮细胞的细胞外基质中重塑GAG,涉及木糖苷的聚糖方法提供了有效促进治疗性血管生成的巨大潜力。
Angiogenesis, the sprouting of new blood vessels from existing vasculature, involves multiple complex biological processes, and it is an essential step for hemostasis, tissue healing and regeneration. Angiogenesis stimulants can ameliorate human disease conditions including limb ischemia, chronic wounds, heart disease, and stroke. The current strategies to improve the bioavailability of pro-angiogenic growth factors, including VEGF and FGF2, have remained largely unsuccessful. This study demonstrates that small molecules, termed click-xylosides, can promote angiogenesis in the in vitro matrigel tube formation assay and the ex ovo chick chorioallantoic membrane assay, depending on their aglycone moieties. Xyloside treatment enhances network connectivity and cell survivability, thereby, maintaining the network structures on matrigel culture for an extended period of time. These effects were achieved via the secreted xyloside-primed glycosaminoglycans (GAG) chains that in part, act through an ERK1/2 mediated signaling pathway. Through the remodeling of GAGs in the extracellular matrix of endothelial cells, the glycan approach, involving xylosides, offers great potential to effectively promote therapeutic angiogenesis.
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发表时间: 2015-04-10
期刊: Molecules (Basel, Switzerland)
影响因子: --
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影响因子: 3
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