Understanding endothelial cell apoptosis: what can the transcriptome, glycome and proteome reveal?

Abstract

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.

CD31 signals confer immune privilege to the vascular endothelium

“…The term "immune privilege" also implies that the protective mechanism(s) apply only to selective cellular components (36). A plethora of signals have been proposed to sustain EC survival in vivo, including adhesion to the basement membrane and to adjacent ECs, growth factors, and survival signals derived from pericytes (6). However, most of these signals selectively prevent mitochondrial apoptosis.…”

“…Although ECs express DRs on their surface, TNF-α and Fas ligand do not activate the extrinsic pathway of apoptosis in ECs efficiently (6). The molecular mechanisms underlying this effect remain elusive.…”

Fibroblast growth factor 2 is a key determinant of vascular sprouting during bovine luteal angiogenesis

“…Interestingly, endothelial cell apoptosis may not only be involved in tissue regression; programmed cell death may also contribute to the formation of vascular-like endothelial cell networks in vitro and blocking apoptosis leads to disrupted vascular growth in vivo (Segura et al 2002, Affara et al 2007). The critical balance of pro-and antiapoptotic signals that must be maintained for appropriate luteal vessel development therefore warrants further investigation.…”

High-throughput bayesian computing machine with reconfigurable hardware

“…Classic machine learning models like hidden Markov models, neural networks, and newer models such as variable-order Markov models can be considered special cases of Bayesian networks. Figure 1 illustrates a realistic dynamic Bayesian gene network generated from apoptosis timecourse data in [15], where dots represent transcripts ("nodes") and arrows between the dots represent potential cause and effect interactions between transcripts ("edges"). Many practical problems, such as the forward/backward algorithm, the Viterbi algorithm, and the Pearl's belief propagation algorithm for Bayesian networks, can be translated into an "inference" formulation, which tries to compute the posterior distribution of hidden nodes given observed nodes in a graphical model, in particular the marginal distribution of each hidden node.…”