Benameur Tarek, Andriantsitohaina Ramaroson, Martínez M Carmen
INSERM U771, CNRS UMR 6214, Faculté de Médecine, Université d'Angers, Haute de Reculée, Angers, France.
Pharmacol Rep. 2009 Jan-Feb;61(1):49-57. doi: 10.1016/s1734-1140(09)70006-4.
In the past, plasma membrane-derived microparticles were considered "cellular dust." According to the literature, circulating levels of microparticles are increased in several cardiovascular diseases associated with inflammation, suggesting that microparticles are linked to deleterious effects such as endothelial dysfunction or thrombosis. However, very recent studies have shown that under several conditions microparticles can transfer biological messages between cells. Indeed, microparticles act as vectors of key information to maintain cell homeostasis or to favor cell repair and induce angiogenesis. For instance, microparticles of platelet origin are able to repair myocardial injury after myocardial infarction. Also, we have shown that engineered microparticles generated from human activated/apoptotic T cells promote angiogenesis through the up-regulation of adhesion proteins and pro-angiogenic factors in human endothelial cells. Interestingly, the effects induced by these microparticles on the formation of capillary-like structures, expression of adhesion molecules, and pro-angiogenic factors are reversed after silencing of the Sonic Hedgehog (Shh) morphogen pathway. In addition, the same type of microparticles is able to induce neo-vascularization in an ischemic hindlimb model. These effects are, at least in part, mediated by Shh and nitric oxide production. Taking into consideration these results and the most recent data concerning the ability of microparticles to transmit genetic information between cells through mRNA transfer, it is plausible that plasma membrane-derived microparticles could serve as tools with veritable therapeutic potential.
过去,质膜衍生的微粒被认为是“细胞尘埃”。根据文献,在几种与炎症相关的心血管疾病中,循环中的微粒水平会升高,这表明微粒与诸如内皮功能障碍或血栓形成等有害影响有关。然而,最近的研究表明,在几种情况下,微粒可以在细胞间传递生物信息。事实上,微粒作为关键信息的载体,可维持细胞内环境稳定,或促进细胞修复并诱导血管生成。例如,血小板来源的微粒能够在心肌梗死后修复心肌损伤。此外,我们已经表明,由人活化/凋亡T细胞产生的工程化微粒通过上调人内皮细胞中的黏附蛋白和促血管生成因子来促进血管生成。有趣的是,在沉默音猬因子(Shh)形态发生途径后,这些微粒对毛细血管样结构形成、黏附分子表达和促血管生成因子的影响会逆转。此外,相同类型的微粒能够在缺血后肢模型中诱导新血管形成。这些作用至少部分是由Shh和一氧化氮的产生介导的。考虑到这些结果以及关于微粒通过mRNA转移在细胞间传递遗传信息能力的最新数据,质膜衍生的微粒有可能成为具有真正治疗潜力的工具。