Affara Muna, Dunmore Benjamin, Savoie Christopher, Imoto Seiya, Tamada Yoshinori, Araki Hiromitsu, Charnock-Jones D Stephen, Miyano Satoru, Print Cristin
Department of Pathology, Cambridge University, Tennis Court Road, Cambridge CB2 1QP, UK.
Philos Trans R Soc Lond B Biol Sci. 2007 Aug 29;362(1484):1469-87. doi: 10.1098/rstb.2007.2129.
Endothelial cell (EC) apoptosis may play an important role in blood vessel development, homeostasis and remodelling. In support of this concept, EC apoptosis has been detected within remodelling vessels in vivo, and inactivation of EC apoptosis regulators has caused dramatic vascular phenotypes. EC apoptosis has also been associated with cardiovascular pathologies. Therefore, understanding the regulation of EC apoptosis, with the goal of intervening in this process, has become a current research focus. The protein-based signalling and cleavage cascades that regulate EC apoptosis are well known. However, the possibility that programmed transcriptome and glycome changes contribute to EC apoptosis has only recently been explored. Traditional bioinformatic techniques have allowed simultaneous study of thousands of molecular signals during the process of EC apoptosis. However, to progress further, we now need to understand the complex cause and effect relationships among these signals. In this article, we will first review current knowledge about the function and regulation of EC apoptosis including the roles of the proteome transcriptome and glycome. Then, we assess the potential for further bioinformatic analysis to advance our understanding of EC apoptosis, including the limitations of current technologies and the potential of emerging technologies such as gene regulatory networks.
内皮细胞(EC)凋亡可能在血管发育、稳态和重塑过程中发挥重要作用。支持这一概念的是,体内重塑血管内已检测到EC凋亡,且EC凋亡调节因子的失活已导致显著的血管表型。EC凋亡也与心血管疾病相关。因此,以干预这一过程为目标,了解EC凋亡的调控机制已成为当前的研究热点。调节EC凋亡的基于蛋白质的信号传导和切割级联反应已为人熟知。然而,程序性转录组和糖组变化促成EC凋亡的可能性直到最近才被探索。传统生物信息学技术能够在EC凋亡过程中同时研究数千种分子信号。然而,为了进一步取得进展,我们现在需要了解这些信号之间复杂的因果关系。在本文中,我们将首先回顾关于EC凋亡功能和调控的现有知识,包括蛋白质组、转录组和糖组的作用。然后,我们评估进一步进行生物信息学分析以深化我们对EC凋亡理解的潜力,包括当前技术的局限性以及基因调控网络等新兴技术的潜力。